bims-mionch 2024-04-14 papers

bims-mionch

Biomed News

on Mitochondrial ion channels

Issue of 2024‒04‒14
nineteen papers selected by
Gun Kim, Seoul National University

Miro GTPases at the Crossroads of Cytoskeletal Dynamics and Mitochondrial Trafficking.
The interplay between sodium/glucose cotransporter type 2 and mitochondrial ionic environment.
MITOCHONDRIA-ASSOCIATED MEMBRANES ARE NOT ALTERED IN IMMUNE CELLS IN T2D.
The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.
Contacting the gut: Mitochondria-associated Endoplasmic Reticulum Membranes in the Enteric Nervous System.
Mechanical regulation of mitochondrial morphodynamics in cancer cells by extracellular microenvironment.
Mitochondrial control of lymphocyte homeostasis.
Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.
Mitochondria transcription and cancer.
Membrane Trafficking Mechanisms and Their Biological Relevance.
Role of mitochondria in pathogenesis and therapy of renal fibrosis.
Mitochondrial Differentiation during Spermatogenesis: Lessons from Drosophila melanogaster.
Dramatic Changes in Mitochondrial Subcellular Location and Morphology Accompany Activation of the CO 2 Concentrating Mechanism.
Mitochondrial fission: a new mechanism of hypertension and cardiovascular remodeling induced by Angiotensin II.
Mitochondrial Permeability Transition, Cell Death and Neurodegeneration.
Targeting VDAC: A potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease.
Special Issue: "Recent Advances in Ion Channels and Ion Channelopathies".
Piezo1, the new actor in cell volume regulation.
Mitochondrial targeting sequence of magnetoreceptor MagR: More than just targeting.

Cells. 2024 Apr 07. pii: 647. [Epub ahead of print]13(7):

Miro GTPases at the Crossroads of Cytoskeletal Dynamics and Mitochondrial Trafficking.

Pontus Aspenström.

  Miro GTPases are key components in the machinery responsible for transporting mitochondria and peroxisomes along microtubules, and also play important roles in regulating calcium homeostasis and organizing contact sites between mitochondria and the endoplasmic reticulum. Moreover, Miro GTPases have been shown to interact with proteins that actively regulate cytoskeletal organization and dynamics, suggesting that these GTPases participate in organizing cytoskeletal functions and organelle transport. Derailed mitochondrial transport is associated with neuropathological conditions such as Parkinson's and Alzheimer's diseases. This review explores our recent understanding of the diverse roles of Miro GTPases under cytoskeletal control, both under normal conditions and during the course of human diseases such as neuropathological disorders.

Keywords:  Miro GTPases; Parkinson’s disease; microtubules; mitochondrial dynamics; neuropathology

DOI:  https://doi.org/10.3390/cells13070647
Mitochondrion. 2024 Apr 08. pii: S1567-7249(24)00036-9. [Epub ahead of print]76 101878

The interplay between sodium/glucose cotransporter type 2 and mitochondrial ionic environment.

Gianmarco Borriello, Veronica Buonincontri, Antonio de Donato, Michele Della Corte, Ilenia Gravina, Pietro Iulianiello, Rashmi Joshi, Pasquale Mone, Giovanna Cacciola, Davide Viggiano.

  Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolytes, such as calcium and hydrogen ions, potassium, and sodium, as well as other osmotic substances, affect the swelling of mitochondria. Intracellular glucose levels may also affect mitochondrial swelling, although the relationship between mitochondrial ion homeostasis and intracellular glucose is poorly understood. This article reviews what is currently known about how the Sodium-Glucose transporter (SGLT) may impact mitochondrial sodium (Na+) homeostasis. SGLTs regulate intracellular glucose and sodium levels and, therefore, interfere with mitochondrial ion homeostasis because mitochondrial Na+ is closely linked to cytoplasmic calcium and sodium dynamics. Recently, a large amount of data has been available on the effects of SGLT2 inhibitors on mitochondria in different cell types, including renal proximal tubule cells, endothelial cells, mesangial cells, podocytes, neuronal cells, and cardiac cells. The current evidence suggests that SGLT inhibitors (SGLTi) may affect mitochondrial dynamics regarding intracellular Sodium and hydrogen ions. Although the regulation of mitochondrial ion channels by SGLTs is still in its infancy, the evidence accumulated thus far of the effect of SGLTi on mitochondrial functions certainly will foster further research in this direction.

Keywords:  Endothelium; Gliflozins; Proximal tubule; SGLT2; Sodium; Swelling

DOI:  https://doi.org/10.1016/j.mito.2024.101878
bioRxiv. 2024 Mar 29. pii: 2024.03.25.586170. [Epub ahead of print]

MITOCHONDRIA-ASSOCIATED MEMBRANES ARE NOT ALTERED IN IMMUNE CELLS IN T2D.

Samantha N Hart, Raji Lenin, Jamie Sturgill, Philip A Kern, Barbara Nikolajczyk.

Metabolism research is increasingly recognizing the contributions of organelle crosstalk to metabolic regulation. Mitochondria-associated membranes (MAMs), which are structures connecting the mitochondria and endoplasmic reticulum (ER), are critical in a myriad of cellular functions linked to cellular metabolism. MAMs control calcium signaling, mitochondrial transport, redox balance, protein folding/degradation, and in some studies, metabolic health. The possibility that MAMs drive changes in cellular function in individuals with Type 2 Diabetes (T2D) is controversial. Although disruptions in MAMs that change the distance between the mitochondria and ER, MAM protein composition, or disrupt downstream signaling, can perpetuate inflammation, one key trait of T2D. However, the full scope of this structure's role in immune cell health and thus T2D-associated inflammation remains unknown. We show that human immune cell MAM proteins and their associated functions are not altered by T2D and thus unlikely to contribute to metaflammation.

DOI: https://doi.org/10.1101/2024.03.25.586170
Cells. 2024 Mar 30. pii: 609. [Epub ahead of print]13(7):

The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.

José M Fuentes, Patricia Morcillo.

  Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases. This review concentrates on papers published in recent years, combined with basic and underexplored research in CL. We capture new findings on its biological functions in the mitochondria, as well as its association with neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Lastly, we explore the potential applications of CL as a biomarker and pharmacological target to mitigate mitochondrial dysfunction.

Keywords:  biological functions; cardiolipin; mitochondria; neurodegenerative diseases; therapeutic applications

DOI:  https://doi.org/10.3390/cells13070609
Contact (Thousand Oaks). 2024 Jan-Dec;7:7 25152564241244941

Contacting the gut: Mitochondria-associated Endoplasmic Reticulum Membranes in the Enteric Nervous System.

Jenny Greig, Giada Delfino, Pascal Derkinderen, Sébastien Paillusson.

  Changes in the connections between the endoplasmic reticulum (ER) and mitochondria, as well as alterations in mitochondria-associated ER membrane (MAM) signalling, have been documented in various neurodegenerative diseases affecting the brain. Despite the growing recognition of the significance of the gut-brain axis in neurodegenerative conditions, there has been no prior investigation into the biology of MAM within the enteric nervous system (ENS). Our recent research reveals, for the first time, the existence of connections between the ER and mitochondria within enteric neurons. Additionally, we observed alterations in the dynamics of these connections in the enteric neurons from a mouse model exhibiting age-related neurodegeneration. These findings provide the first detailed characterization of MAM in the ENS under physiological conditions and in a mouse model of age-associated neurodegeneration and shed new light on the potential role of enteric MAM in the context of neurodegenerative disorders.

Keywords:  Alzheimer's disease; Parkinson's disease; ageing; enteric nervous system; mitochondria-associated ER membranes

DOI:  https://doi.org/10.1177/25152564241244941
Biomater Biosyst. 2024 Jun;14 100093

Mechanical regulation of mitochondrial morphodynamics in cancer cells by extracellular microenvironment.

Mariia Lunova, Milan Jirsa, Alexandr Dejneka, Gareth John Sullivan, Oleg Lunov.

  Recently, it has been recognized that physical abnormalities (e.g. elevated solid stress, elevated interstitial fluid pressure, increased stiffness) are associated with tumor progression and development. Additionally, these mechanical forces originating from tumor cell environment through mechanotransduction pathways can affect metabolism. On the other hand, mitochondria are well-known as bioenergetic, biosynthetic, and signaling organelles crucial for sensing stress and facilitating cellular adaptation to the environment and physical stimuli. Disruptions in mitochondrial dynamics and function have been found to play a role in the initiation and advancement of cancer. Consequently, it is logical to hypothesize that mitochondria dynamics subjected to physical cues may play a pivotal role in mediating tumorigenesis. Recently mitochondrial biogenesis and turnover, fission and fusion dynamics was linked to mechanotransduction in cancer. However, how cancer cell mechanics and mitochondria functions are connected, still remain poorly understood. Here, we discuss recent studies that link mechanical stimuli exerted by the tumor cell environment and mitochondria dynamics and functions. This interplay between mechanics and mitochondria functions may shed light on how mitochondria regulate tumorigenesis.

Keywords:  Cancer; Mechanotransduction; Mitochondria; Mitochondrial dynamics; Tumor metabolism

DOI:  https://doi.org/10.1016/j.bbiosy.2024.100093
Semin Cell Dev Biol. 2024 Apr 11. pii: S1084-9521(24)00031-4. [Epub ahead of print]161-162 42-53

Mitochondrial control of lymphocyte homeostasis.

Yavuz F Yazicioglu, Robert J Mitchell, Alexander J Clarke.

  Mitochondria play a multitude of essential roles within mammalian cells, and understanding how they control immunity is an emerging area of study. Lymphocytes, as integral cellular components of the adaptive immune system, rely on mitochondria for their function, and mitochondria can dynamically instruct their differentiation and activation by undergoing rapid and profound remodelling. Energy homeostasis and ATP production are often considered the primary functions of mitochondria in immune cells; however, their importance extends across a spectrum of other molecular processes, including regulation of redox balance, signalling pathways, and biosynthesis. In this review, we explore the dynamic landscape of mitochondrial homeostasis in T and B cells, and discuss how mitochondrial disorders compromise adaptive immunity.

Keywords:  Adaptive immunity; B cells; Lymphocytes; Mitochondria; T cells

DOI:  https://doi.org/10.1016/j.semcdb.2024.03.002
Adv Pharm Bull. 2024 Mar;14(1): 147-160

Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.

Pranay Wal, Ankita Wal, Himangi Vig, Danish Mahmood, Mohd Masih Uzzaman Khan.

  Purpose: Both aging and neurodegenerative illnesses are thought to be influenced by mitochondrial malfunction and free radical formation. Deformities of the energy metabolism, mitochondrial genome polymorphisms, nuclear DNA genetic abnormalities associated with mitochondria, modifications of mitochondrial fusion or fission, variations in shape and size, variations in transit, modified mobility of mitochondria, transcription defects, and the emergence of misfolded proteins associated with mitochondria are all linked to Parkinson's disease.Methods: This review is a condensed compilation of data from research that has been published between the years of 2014 and 2022, using search engines like Google Scholar, PubMed, and Scopus.
Results: Mitochondrial transplantation is a one-of-a-kind treatment for mitochondrial diseases and deficits in mitochondrial biogenesis. The replacement of malfunctioning mitochondria with transplanted viable mitochondria using innovative methodologies has shown promising outcomes as a cure for Parkinson's, involving tissue sparing coupled with enhanced energy generation and lower oxidative damage. Numerous mitochondria-targeted therapies, including mitochondrial gene therapy, redox therapy, and others, have been investigated for their effectiveness and potency.
Conclusion: The development of innovative therapeutics for mitochondria-directed treatments in Parkinson's disease may be aided by optimizing mitochondrial dynamics. Many neurological diseases have been studied in animal and cellular models, and it has been found that mitochondrial maintenance can slow the death of neuronal cells. It has been hypothesized that drug therapies for neurodegenerative diseases that focus on mitochondrial dysfunction will help to delay the onset of neuronal dysfunction.

Keywords:  Mitochondrial dynamics; Mitochondrial therapeutics; Mitochondrial transplantation; Neurodegeneration; Parkinson’s disease

DOI:  https://doi.org/10.34172/apb.2024.019
Cell Death Discov. 2024 Apr 08. 10(1): 168

Mitochondria transcription and cancer.

Tang Lei, Yu Rui, Zhou Xiaoshuang, Zhang Jinglan, Zhang Jihong.

Mitochondria are major organelles involved in several processes related to energy supply, metabolism, and cell proliferation. The mitochondria function is transcriptionally regulated by mitochondria DNA (mtDNA), which encodes the key proteins in the electron transport chain that is indispensable for oxidative phosphorylation (OXPHOS). Mitochondrial transcriptional abnormalities are closely related to a variety of human diseases, such as cardiovascular diseases, and diabetes. The mitochondria transcription is regulated by the mtDNA, mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERFs). Dysregulation of these factors directly leads to altered expression of mtDNA in tumor cells, resulting in cellular metabolic reprogramming and mitochondrial dysfunction. This dysregulation plays a role in modulating tumor progression. Therefore, understanding the role of mitochondrial transcription in cancer can have implications for cancer diagnosis, prognosis, and treatment. Targeting mitochondrial transcription or related pathways may provide potential therapeutic strategies for cancer treatment. Additionally, assessing mitochondrial transcriptional profiles or biomarkers in cancer cells or patient samples may offer diagnostic or prognostic information.

DOI: https://doi.org/10.1038/s41420-024-01926-3
Arch Razi Inst. 2023 Oct;78(5): 1397-1412

Membrane Trafficking Mechanisms and Their Biological Relevance.

O Adeoye Akinwunmi.

  Most chemicals expressed in mammalian cells have complex delivery and transport mechanisms to get to the right intracellular sites. One of these mechanisms transports most transmembrane proteins, as well as almost all secreted proteins, from the endoplasmic reticulum, where they are formed, to their final location. Nearly all eukaryotic cells have a membrane trafficking mechanism that is both a prominent and critical component. This system, which consists of dynamically coupled compartments, supports the export and uptake of extracellular material, remodeling and signaling at the cellular interface, intracellular alignment, and maintenance of internal compartmentalization (organelles). In animal cells, this system enables both regular cellular activities and specialized tasks, such as neuronal transmission and hormone control. Human diseases, including neurodegenerative diseases, such as Alzheimer's disease, heart disease, and cancer, are associated with the dysfunction or dysregulation of the membrane trafficking system. Treatment and cure of human diseases depends on understanding the cellular and molecular principles underlying membrane trafficking pathways. A single gene mutation or mutations that result in impaired membrane trafficking cause a range of clinical disorders that are the result of changes in cellular homeostasis. Other eukaryotic organisms with significant economic and agricultural value, such as plants and fungi, also depend on the membrane trafficking system for their survival. In this review, we focused on the major human diseases associated with the process of membrane trafficking, providing a broad overview of membrane trafficking.

Keywords:   Endocytosis; Exocytosis; Membrane proteins; Membrane trafficking; Vesicular transport

DOI:  https://doi.org/10.22092/ARI.2023.78.5.1397
Metabolism. 2024 Apr 10. pii: S0026-0495(24)00139-2. [Epub ahead of print] 155913

Role of mitochondria in pathogenesis and therapy of renal fibrosis.

Xiaodong Zhao, Yunkuo Li, Jinyu Yu, Haolin Teng, Shouwang Wu, Yishu Wang, Honglan Zhou, Faping Li.

  Renal fibrosis, specifically tubulointerstitial fibrosis, represents the predominant pathological consequence observed in the context of progressive chronic kidney conditions. The pathogenesis of renal fibrosis encompasses a multifaceted interplay of mechanisms, including but not limited to interstitial fibroblast proliferation, activation, augmented production of extracellular matrix (ECM) components, and impaired ECM degradation. Notably, mitochondria, the intracellular organelles responsible for orchestrating biological oxidation processes in mammalian cells, assume a pivotal role within this intricate milieu. Mitochondrial dysfunction, when manifest, can incite a cascade of events, including inflammatory responses, perturbed mitochondrial autophagy, and associated processes, ultimately culminating in the genesis of renal fibrosis. This comprehensive review endeavors to furnish an exegesis of mitochondrial pathophysiology and biogenesis, elucidating the precise mechanisms through which mitochondrial aberrations contribute to the onset and progression of renal fibrosis. We explored how mitochondrial dysfunction, mitochondrial cytopathy and mitochondrial autophagy mediate ECM deposition and renal fibrosis from a multicellular perspective of mesangial cells, endothelial cells, podocytes, macrophages and fibroblasts. Furthermore, it succinctly encapsulates the most recent advancements in the realm of mitochondrial-targeted therapeutic strategies aimed at mitigating renal fibrosis.

Keywords:  Biogenesis; Extracellular matrix; Mitochondria; Renal fibrosis; Therapies

DOI:  https://doi.org/10.1016/j.metabol.2024.155913
Int J Mol Sci. 2024 Apr 03. pii: 3980. [Epub ahead of print]25(7):

Mitochondrial Differentiation during Spermatogenesis: Lessons from Drosophila melanogaster.

Viktor Vedelek, Ferenc Jankovics, János Zádori, Rita Sinka.

  Numerous diseases can arise as a consequence of mitochondrial malfunction. Hence, there is a significant focus on studying the role of mitochondria in cancer, ageing, neurodegenerative diseases, and the field of developmental biology. Mitochondria could exist as discrete organelles in the cell; however, they have the ability to fuse, resulting in the formation of interconnected reticular structures. The dynamic changes between these forms correlate with mitochondrial function and mitochondrial health, and consequently, there is a significant scientific interest in uncovering the specific molecular constituents that govern these transitions. Moreover, the specialized mitochondria display a wide array of variable morphologies in their cristae formations. These inner mitochondrial structures are closely associated with the specific functions performed by the mitochondria. In multiple cases, the presence of mitochondrial dysfunction has been linked to male sterility, as it has been observed to cause a range of abnormal spermatogenesis and sperm phenotypes in different species. This review aims to elucidate the dynamic alterations and functions of mitochondria in germ cell development during the spermatogenesis of Drosophila melanogaster.

Keywords:  Drosophila melanogaster; mitochondria; mitochondrial differentiation; nebenkern; paracristalline material; spermatogenesis; testis

DOI:  https://doi.org/10.3390/ijms25073980
bioRxiv. 2024 Mar 27. pii: 2024.03.25.586705. [Epub ahead of print]

Dramatic Changes in Mitochondrial Subcellular Location and Morphology Accompany Activation of the CO 2 Concentrating Mechanism.

Justin Findinier, Lydia-Marie Joubert, Michael F Schmid, Andrey Malkovskiy, Wah Chiu, Adrien Burlacot, Arthur R Grossman.

Dynamic changes in intracellular ultrastructure can be critical for the ability of organisms to acclimate to environmental conditions. Microalgae, which are responsible for ∼50% of global photosynthesis, compartmentalize their Rubisco into a specialized structure known as the pyrenoid when the cells experience limiting CO 2 conditions; this compartmentalization appears to be a component of the CO 2 Concentrating Mechanism (CCM), which facilitates photosynthetic CO 2 fixation as environmental levels of inorganic carbon (Ci) decline. Changes in the spatial distribution of mitochondria in green algae have also been observed under CO 2 limiting conditions, although a role for this reorganization in CCM function remains unclear. We used the green microalgae Chlamydomonas reinhardtii to monitor changes in the position and ultrastructure of mitochondrial membranes as cells transition between high CO 2 (HC) and Low/Very Low CO 2 (LC/VLC). Upon transferring cells to VLC, the mitochondria move from a central to a peripheral location, become wedged between the plasma membrane and chloroplast envelope, and mitochondrial membranes orient in parallel tubular arrays that extend from the cell's apex to its base. We show that these ultrastructural changes require protein and RNA synthesis, occur within 90 min of shifting cells to VLC conditions, correlate with CCM induction and are regulated by the CCM master regulator CIA5. The apico-basal orientation of the mitochondrial membrane, but not the movement of the mitochondrion to the cell periphery, is dependent on microtubules and the MIRO1 protein, which is involved in membrane-microtubule interactions. Furthermore, blocking mitochondrial electron transport in VLC acclimated cells reduces the cell's affinity for inorganic carbon. Overall, our results suggest that CIA5-dependent mitochondrial repositioning/reorientation functions in integrating cellular architecture and energetics with CCM activities and invite further exploration of how intracellular architecture can impact fitness under dynamic environmental conditions.

DOI: https://doi.org/10.1101/2024.03.25.586705
Hypertens Res. 2024 Apr 10.

Mitochondrial fission: a new mechanism of hypertension and cardiovascular remodeling induced by Angiotensin II.

Kohei Ueda, Shigeru Shibata.



Keywords:  Fission; Mitochondria; Vascular dysfunction

DOI:  https://doi.org/10.1038/s41440-024-01670-2
Cells. 2024 Apr 08. pii: 648. [Epub ahead of print]13(7):

Mitochondrial Permeability Transition, Cell Death and Neurodegeneration.

Artyom Y Baev, Andrey Y Vinokurov, Elena V Potapova, Andrey V Dunaev, Plamena R Angelova, Andrey Y Abramov.

  Neurodegenerative diseases are chronic conditions occurring when neurons die in specific brain regions that lead to loss of movement or cognitive functions. Despite the progress in understanding the mechanisms of this pathology, currently no cure exists to treat these types of diseases: for some of them the only help is alleviating the associated symptoms. Mitochondrial dysfunction has been shown to be involved in the pathogenesis of most the neurodegenerative disorders. The fast and transient permeability of mitochondria (the mitochondrial permeability transition, mPT) has been shown to be an initial step in the mechanism of apoptotic and necrotic cell death, which acts as a regulator of tissue regeneration for postmitotic neurons as it leads to the irreparable loss of cells and cell function. In this study, we review the role of the mitochondrial permeability transition in neuronal death in major neurodegenerative diseases, covering the inductors of mPTP opening in neurons, including the major ones-free radicals and calcium-and we discuss perspectives and difficulties in the development of a neuroprotective strategy based on the inhibition of mPTP in neurodegenerative disorders.

Keywords:  astrocyte; cell death; mitochondrial permeability transition; neurodegeneration; neuron

DOI:  https://doi.org/10.3390/cells13070648
Brain Res. 2024 Apr 08. pii: S0006-8993(24)00174-4. [Epub ahead of print]1835 148920

Targeting VDAC: A potential therapeutic approach for mitochondrial dysfunction in Alzheimer's disease.

Yaqian Yang, Xiaotao Jia, Xinmao Yang, Jie Wang, Yan Fang, Xiaoping Ying, Meiqian Zhang, Jing Wei, Yanfang Pan.

  Mitochondrial dysfunction has been implicated in the pathogenesis of Alzheimer's disease, a neurodegenerative disorder characterized by progressive cognitive decline. Voltage-dependent anion channel (VDAC), a protein located in the outer mitochondrial membrane, plays a critical role in regulating mitochondrial function and cellular energy metabolism. Recent studies have identified VDAC as a potential therapeutic target for Alzheimer's disease. This article aims to provide an overview of the role of VDAC in mitochondrial dysfunction, its association with Alzheimer's disease, and the potential of targeting VDAC for developing novel therapeutic interventions. Understanding the involvement of VDAC in Alzheimer's disease may pave the way for the development of effective treatments that can restore mitochondrial function and halt disease progression.

Keywords:  Alzheimer’s disease; Mitochondrial dynamics; Voltage-Dependent Anion Channel

DOI:  https://doi.org/10.1016/j.brainres.2024.148920
Int J Mol Sci. 2024 Mar 22. pii: 3598. [Epub ahead of print]25(7):

Special Issue: "Recent Advances in Ion Channels and Ion Channelopathies".

Deanne H Hryciw.

The aim of this special issue was to showcase recent advanced in understanding ion channel function and dysfunction associated with disease [...].

DOI: https://doi.org/10.3390/ijms25073598
Pflugers Arch. 2024 Apr 06.

Piezo1, the new actor in cell volume regulation.

A Michelucci, L Catacuzzeno.

  All animal cells control their volume through a complex set of mechanisms, both to counteract osmotic perturbations of the environment and to enable numerous vital biological processes, such as proliferation, apoptosis, and migration. The ability of cells to adjust their volume depends on the activity of ion channels and transporters which, by moving K+, Na+, and Cl- ions across the plasma membrane, generate the osmotic gradient that drives water in and out of the cell. In 2010, Patapoutian's group identified a small family of evolutionarily conserved, Ca2+-permeable mechanosensitive channels, Piezo1 and Piezo2, as essential components of the mechanically activated current that mediates mechanotransduction in vertebrates. Piezo1 is expressed in several tissues and its opening is promoted by a wide range of mechanical stimuli, including membrane stretch/deformation and osmotic stress. Piezo1-mediated Ca2+ influx is used by the cell to convert mechanical forces into cytosolic Ca2+ signals that control diverse cellular functions such as migration and cell death, both dependent on changes in cell volume and shape. The crucial role of Piezo1 in the regulation of cell volume was first demonstrated in erythrocytes, which need to reduce their volume to pass through narrow capillaries. In HEK293 cells, increased expression of Piezo1 was found to enhance the regulatory volume decrease (RVD), the process whereby the cell re-establishes its original volume after osmotic shock-induced swelling, and it does so through Ca2+-dependent modulation of the volume-regulated anion channels. More recently we reported that Piezo1 controls the RVD in glioblastoma cells via the modulation of Ca2+-activated K+ channels. To date, however, the mechanisms through which this mechanosensitive channel controls cell volume and maintains its homeostasis have been poorly investigated and are still far from being understood. The present review aims to provide a broad overview of the literature discussing the recent advances on this topic.

Keywords:  Cell death; KCa channels; Migration; Piezo1; Regulatory volume decrease; VRAC

DOI:  https://doi.org/10.1007/s00424-024-02951-y
Zool Res. 2024 May 18. pii: 2095-8137(2024)03-0468-10. [Epub ahead of print]45(3): 468-477

Mitochondrial targeting sequence of magnetoreceptor MagR: More than just targeting.

Yanqi Zhang, Peng Zhang, Junjun Wang, Jing Zhang, Tianyang Tong, Xiujuan Zhou, Yajie Zhou, Mengke Wei, Chuanlin Feng, Jinqian Li, Xin Zhang, Can Xie, Tiantian Cai.

  Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties. MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation. Although the N-terminal sequences of MagR vary among species, their specific function remains unknown. In the present study, we found that the N-terminal sequences of pigeon MagR, previously thought to serve as a mitochondrial targeting signal (MTS), were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound. Moreover, the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex. Thus, the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting. These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

Keywords:  Iron-sulfur cluster; Magnetoreceptor (MagR); Mitochondrial targeting signal; N-terminal sequence

DOI:  https://doi.org/10.24272/j.issn.2095-8137.2023.385