bims-mikwok 2022-11-20 papers

bims-mikwok

Biomed News

on Mitochondrial quality control

Issue of 2022‒11‒20
fourteen papers selected by
Avinash N. Mukkala, University of Toronto

The interaction between E3 ubiquitin ligase Parkin and mitophagy receptor PHB2 links inner mitochondrial membrane ubiquitination to efficient mitophagy.
Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation.
BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia.
Delivery of mitoceuticals or respiratory competent mitochondria to sites of neurotrauma.
Carbon Monoxide Stimulates Both Mitophagy And Mitochondrial Biogenesis to Mediate Protection Against Oxidative Stress in Astrocytes.
Selection of red fluorescent protein for genetic labeling of mitochondria and intercellular transfer of viable mitochondria.
Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization.
LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus.
Mitochondrial Transplantation Therapy against Ifosfamide Induced Toxicity on Rat Renal Proximal Tubular Cells.
Nonstop mRNAs generate a ground state of mitochondrial gene expression noise.
Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.
Remote Ischemic Pre-Conditioning (RIPC).
Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome.
Organelle homeostasis: from cellular mechanisms to disease.

J Biol Chem. 2022 Nov 12. pii: S0021-9258(22)01147-4. [Epub ahead of print] 102704

The interaction between E3 ubiquitin ligase Parkin and mitophagy receptor PHB2 links inner mitochondrial membrane ubiquitination to efficient mitophagy.

Shan Sun, Hongyu Hou, Guoqiang Ma, Qilian Ma, Ningning Li, Li Zhang, Chunsheng Dong, Mian Cao, Kin Yip Tam, Zheng Ying, Hongfeng Wang.

  The autophagic clearance of mitochondria has been defined as mitophagy, which is triggered by mitochondrial damage and serves as a major pathway for mitochondrial homeostasis and cellular quality control. PINK1 and Parkin-mediated mitophagy is the most extensively studied form of mitophagy, which has been linked to the pathogenesis of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current paradigm of this particular mitophagy pathway is that the ubiquitination of the outer mitochondrial membrane is the key step to enable the recognition of damaged mitochondria by the core autophagic component autophagosome. However, whether the inner mitochondrial membrane (IMM) is ubiquitinated by Parkin and its contribution to sufficient mitophagy remain unclear. Here, using molecular, cellular, and biochemical approaches, we report that prohibitin 2 (PHB2), an essential IMM receptor for mitophagy, is ubiquitinated by Parkin and thereby gains higher affinity to the autophagosome during mitophagy. Our findings suggest that Parkin directly binds to PHB2 through its RING1 domain and promotes K11- and K33-linked ubiquitination on K142/K200 sites of PHB2, thereby enhancing the interaction between PHB2 and MAP1LC3B/LC3B. Interestingly and importantly, our study allows us to propose a novel model in which IMM protein PHB2 serves as both a receptor and a ubiquitin-mediated base for autophagosome recruitment to ensure efficient mitophagy.

Keywords:  MAP1LC3B/LC3B; PHB2; Parkin; mitophagy; ubiquitination

DOI:  https://doi.org/10.1016/j.jbc.2022.102704
Proc Natl Acad Sci U S A. 2022 Nov 22. 119(47): e2210730119

Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation.

Takaya Ishihara, Reiko Ban-Ishihara, Azusa Ota, Naotada Ishihara.

  Mitochondria have their own DNA (mtDNA), which encodes essential respiratory subunits. Under live imaging, mitochondrial nucleoids, composed of several copies of mtDNA and DNA-binding proteins, such as mitochondrial transcription factor A (TFAM), actively move inside mitochondria and change the morphology, in concert with mitochondrial membrane fission. Here we found the mitochondrial inner membrane-anchored AAA-ATPase protein ATAD3A mediates the nucleoid dynamics. Its ATPase domain exposed to the matrix binds directly to TFAM and mediates nucleoid trafficking along mitochondria by ATP hydrolysis. Nucleoid trafficking also required ATAD3A oligomerization via an interaction between the coiled-coil domains in intermembrane space. In ATAD3A deficiency, impaired nucleoid trafficking repressed the clustered and enlarged nucleoids observed in mitochondrial fission-deficient cells resulted in dispersed distribution of small nucleoids observed throughout the mitochondrial network, and this enhanced respiratory complex formation. Thus, mitochondrial fission and nucleoid trafficking cooperatively determine the size, number, and distribution of nucleoids in mitochondrial network, which should modulate respiratory complex formation.

Keywords:  ATAD3A; Drp1; mitochondrial fission; mtDNA nucleoid; respiratory complex

DOI:  https://doi.org/10.1073/pnas.2210730119
Cell Death Dis. 2022 Nov 17. 13(11): 966

BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia.

Yun-Ling He, Jian Li, Sheng-Hui Gong, Xiang Cheng, Ming Zhao, Yan Cao, Tong Zhao, Yong-Qi Zhao, Ming Fan, Hai-Tao Wu, Ling-Ling Zhu, Li-Ying Wu.

Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.

DOI: https://doi.org/10.1038/s41419-022-05418-z
Mitochondrion. 2022 Nov 09. pii: S1567-7249(22)00090-3. [Epub ahead of print]68 10-14

Delivery of mitoceuticals or respiratory competent mitochondria to sites of neurotrauma.

Samir P Patel, Felicia M Michael, Jenna L Gollihue, W Brad Hubbard, Patrick G Sullivan, Alexander G Rabchevsky.

  Herein, we review evidence that targeting mitochondrial dysfunction with 'mitoceuticals' is an effective neuroprotective strategy following neurotrauma, and that isolated exogenous mitochondria can be effectively transplanted into host spinal cord parenchyma to increase overall cellular metabolism. We further discuss control measures to ensure greatest potential for mitochondrial transfer, notably using erodible thermogelling hydrogels to deliver respiratory competent mitochondria to the injured spinal cord.

Keywords:  Bioenergetics; Hydrogel; Metabolism; Mitochondria; Oxidative phosphorylation; Spinal cord; Transplantation

DOI:  https://doi.org/10.1016/j.mito.2022.11.001
Mol Neurobiol. 2022 Nov 15.

Carbon Monoxide Stimulates Both Mitophagy And Mitochondrial Biogenesis to Mediate Protection Against Oxidative Stress in Astrocytes.

Cláudia Figueiredo-Pereira, Beatriz Villarejo-Zori, Pedro C Cipriano, Diana Tavares, Ignacio Ramírez-Pardo, Patricia Boya, Helena L A Vieira.

  Astrocytes are key glial cells for the metabolic and functional support of the brain. Mitochondrial quality control (MQC), in particular the balance between mitophagy and mitochondrial biogenesis, is a major event for the maintenance of cellular homeostasis. Carbon monoxide (CO) is an endogenous gasotransmitter that inhibits cell death and inflammation by targeting mitochondria. It is well established that CO promotes cytoprotection by increasing mitochondrial population and metabolism (oxidative phosphorylation). Thus, it is hypothesized that CO-induced cytoprotection may also be mediated by the balance between mitophagy and mitochondrial biogenesis. Herein, the carbon monoxide releasing molecule-A1 (CORM-A1) was used in primary cultures of astrocytes to assess CO role on mitochondrial turnover. PINK1/Parkin-dependent mitophagy was stimulated by CORM-A1 following 1 h of treatment. While at 24 h after treatment, CORM-A1 increased mitochondrial population, which may indicate mitochondrial biogenesis. In fact, mitochondrial biogenesis was confirmed by the enhancement of PGC-1α expression that upregulates several mitochondrial transcription factors. Furthermore, inhibition of mitophagy by knocking down PINK1 expression reverted CO-induced mitochondrial biogenesis, indicating that mitochondrial turnover is dependent on modulation of mitophagy. Finally, CORM-A1 prevented astrocytic cell death induced by oxidative stress in a mitophagy-dependent manner. In fact, whenever PINK1 was knocked down, CORM-A1-induced cytoprotection was lost. In summary, CORM-A1 stimulates mitochondrial turnover, which in turn prevents astrocytic cell death. CO cytoprotection depends on increasing mitochondrial population and on eliminating dysfunctional mitochondria.

Keywords:  Astrocytes; Carbon monoxide; Cell death; Mitochondrial biogenesis; Mitophagy; PINK1

DOI:  https://doi.org/10.1007/s12035-022-03108-7
Sci Rep. 2022 Nov 18. 12(1): 19841

Selection of red fluorescent protein for genetic labeling of mitochondria and intercellular transfer of viable mitochondria.

Isamu Taiko, Chika Takano, Masayuki Nomoto, Shingo Hayashida, Kazunori Kanemaru, Toshio Miki.

The phenomenon of intercellular mitochondrial transfer has attracted great attention in various fields of research, including stem cell biology. Elucidating the mechanism of mitochondrial transfer from healthy stem cells to cells with mitochondrial dysfunction may lead to the development of novel stem cell therapies to treat mitochondrial diseases, among other advances. To visually evaluate and analyze the mitochondrial transfer process, dual fluorescent labeling systems are often used to distinguish the mitochondria of donor and recipient cells. Although enhanced green fluorescent protein (EGFP) has been well-characterized for labeling mitochondria, other colors of fluorescent protein have been less extensively evaluated in the context of mitochondrial transfer. Here, we generated different lentiviral vectors with mitochondria-targeted red fluorescent proteins (RFPs), including DsRed, mCherry (both from Discosoma sp.) Kusabira orange (mKOκ, from Verrillofungia concinna), and TurboRFP (from Entacmaea quadricolor). Among these proteins, mitochondria-targeted DsRed and its variant mCherry often generated bright aggregates in the lysosome while other proteins did not. We further validated that TurboRFP-labeled mitochondria were successfully transferred from amniotic epithelial cells, one of the candidates for donor stem cells, to mitochondria-damaged recipient cells without losing the membrane potential. Our study provides new insight into the genetic labeling of mitochondria with red fluorescent proteins, which may be utilized to analyze the mechanism of intercellular mitochondrial transfer.

DOI: https://doi.org/10.1038/s41598-022-24297-0
iScience. 2022 Nov 18. 25(11): 105447

Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization.

M A Neginskaya, S E Morris, E V Pavlov.

  An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes.

Keywords:  Cell biology; Functional aspects of cell biology; Molecular biology

DOI:  https://doi.org/10.1016/j.isci.2022.105447
EMBO J. 2022 Nov 18. e112006

LUBAC assembles a ubiquitin signaling platform at mitochondria for signal amplification and transport of NF-κB to the nucleus.

Zhixiao Wu, Lena A Berlemann, Verian Bader, Dominik A Sehr, Eva Dawin, Alberto Covallero, Jens Meschede, Lena Angersbach, Cathrin Showkat, Jonas B Michaelis, Christian Münch, Bettina Rieger, Dmitry Namgaladze, Maria Georgina Herrera, Fabienne C Fiesel, Wolfdieter Springer, Marta Mendes, Jennifer Stepien, Katalin Barkovits, Katrin Marcus, Albert Sickmann, Gunnar Dittmar, Karin B Busch, Dietmar Riedel, Marisa Brini, Jörg Tatzelt, Tito Cali, Konstanze F Winklhofer.

  Mitochondria are increasingly recognized as cellular hubs to orchestrate signaling pathways that regulate metabolism, redox homeostasis, and cell fate decisions. Recent research revealed a role of mitochondria also in innate immune signaling; however, the mechanisms of how mitochondria affect signal transduction are poorly understood. Here, we show that the NF-κB pathway activated by TNF employs mitochondria as a platform for signal amplification and shuttling of activated NF-κB to the nucleus. TNF treatment induces the recruitment of HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), and its substrate NEMO to the outer mitochondrial membrane, where M1- and K63-linked ubiquitin chains are generated. NF-κB is locally activated and transported to the nucleus by mitochondria, leading to an increase in mitochondria-nucleus contact sites in a HOIP-dependent manner. Notably, TNF-induced stabilization of the mitochondrial kinase PINK1 furthermore contributes to signal amplification by antagonizing the M1-ubiquitin-specific deubiquitinase OTULIN. Overall, our study reveals a role for mitochondria in amplifying TNF-mediated NF-κB activation, both serving as a signaling platform, as well as a transport mode for activated NF-κB to the nuclear.

Keywords:  HOIP; NEMO; OTULIN; PINK1; ubiquitin

DOI:  https://doi.org/10.15252/embj.2022112006
Drug Res (Stuttg). 2022 Nov 17.

Mitochondrial Transplantation Therapy against Ifosfamide Induced Toxicity on Rat Renal Proximal Tubular Cells.

Abdollah Arjmand, Melika Mashhadi, Armin Kaveh, Farzaneh Kamranfar, Enayatollah Seydi, Jalal Pourahmad.

Mitochondrial dysfunction is a basic mechanism leading to drug nephrotoxicity. Replacement of defective mitochondria with freshly isolated mitochondria is potentially a comprehensive tool to inhibit cytotoxicity induced by ifosfamide on renal proximal tubular cells (RPTCs). We hypothesize that the direct exposure of freshly isolated mitochondria into RPTCs affected by ifosfamide might restore mitochondrial function and reduce cytotoxicity. So, the aim of this study was to assess the protective effect of freshly isolated mitochondrial transplantation against ifosfamide-induced cytotoxicity in RPTCs. Therefore, the suspension of rat RPTCs (106 cells/ml) in Earle's solution with the pH of 7.4 at 37°C was incubated for 2 h after ifosfamide (4 mM) addition. Fresh mitochondria were isolated from the rat kidney and diluted to the needed concentrations at 4°C. The media containing suspended RPTCs was replaced with mitochondrial-supplemented media, which was exposed to cells for 4 hours in flasks-rotating in a water bath at 37°C. Statistical analysis demonstrated that mitochondrial administration reduced cytotoxicity, lipid peroxidation (LPO), reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, lysosomal membrane damage, extracellular oxidized glutathione (GSSG) level, and caspase-3 activity induced by ifosfamide in rat RPTCs. Moreover, mitochondrial transplantation increased the intracellular reduced glutathione (GSH) level in RPTCs affected by ifosfamide. According to the current study, mitochondrial transplantation is a promising therapeutic method in xenobiotic-caused nephrotoxicity pending successful complementary in vivo and clinical studies.

DOI: https://doi.org/10.1055/a-1967-2066
Sci Adv. 2022 Nov 16. 8(46): eabq5234

Nonstop mRNAs generate a ground state of mitochondrial gene expression noise.

Kah Ying Ng, Guleycan Lutfullahoglu Bal, Uwe Richter, Omid Safronov, Lars Paulin, Cory D Dunn, Ville O Paavilainen, Julie Richer, William G Newman, Robert W Taylor, Brendan J Battersby.

A stop codon within the mRNA facilitates coordinated termination of protein synthesis, releasing the nascent polypeptide from the ribosome. This essential step in gene expression is impeded with transcripts lacking a stop codon, generating nonstop ribosome complexes. Here, we use deep sequencing to investigate sources of nonstop mRNAs generated from the human mitochondrial genome. We identify diverse types of nonstop mRNAs on mitochondrial ribosomes that are resistant to translation termination by canonical release factors. Failure to resolve these aberrations by the mitochondrial release factor in rescue (MTRFR) imparts a negative regulatory effect on protein synthesis that is associated with human disease. Our findings reveal a source of underlying noise in mitochondrial gene expression and the importance of responsive ribosome quality control mechanisms for cell fitness and human health.

DOI: https://doi.org/10.1126/sciadv.abq5234
Sci Rep. 2022 Nov 17. 12(1): 19805

Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.

Isabella C Hirako, Maísa Mota Antunes, Rafael Machado Rezende, Natália Satchiko Hojo-Souza, Maria Marta Figueiredo, Thomaz Dias, Helder Nakaya, Gustavo Batista Menezes, Ricardo Tostes Gazzinelli.

Kupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections. Similar to patients, infection with Plasmodium chabaudi induced acute liver damage as determined by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. This was associated with accumulation of hemozoin, increased of proinflammatory response and impaired bacterial and viral clearance, which led to pathogen spread to other organs. In line with this, mice infected with Plasmodium had enhanced mortality during secondary infections, which was associated with increased production of mitochondrial superoxide, lipid peroxidation and increased free iron within KCs-hallmarks of cell death by ferroptosis. Therefore, we revealed that accumulation of iron with KCs, triggered by uptake of circulating hemozoin, is a novel mechanism of macrophage depletion and liver inflammation during malaria, providing novel insights on host susceptibility to secondary infections. Malaria can cause severe liver damage, along with depletion of liver macrophages, which can predispose individuals to secondary infections and enhance the chances of death.

DOI: https://doi.org/10.1038/s41598-022-23858-7
Methods Mol Biol. 2023 ;2597 11-18

Remote Ischemic Pre-Conditioning (RIPC).

Kyung Eun Lee, Jongsoo Kim, Ki Ho Park, Jianjie Ma, Hua Zhu.

  Ischemic pre-conditioning has been shown to protect hearts against ischemia/reperfusion (I/R)-induced cardiac injury. However, it is not feasible in clinic. Many researchers have tried to introduce brief I/R in skeletal muscle to mimic cardiac ischemic pre-conditioning, called remote ischemia pre-conditioning (RIPC). Studies from our group and other groups have shown that RIPC induces the release of cytokines from skeletal muscle (myokines) for tissue protection. Myokines play a central role in repair, inflammatory, and immune responses after injury. Thus, the detailed protocol for RIPC might be useful for researchers to study mechanisms underlying RIPC-mediated tissue protection and crosstalk. Here, we describe a detailed RIPC protocol and show MG53 secretion after RIPC into the blood.

Keywords:  MG53; Myokine; Remote ischemia pre-conditioning (RIPC); Tissue crosstalk

DOI:  https://doi.org/10.1007/978-1-0716-2835-5_2
EBioMedicine. 2022 Nov;pii: S2352-3964(22)00493-5. [Epub ahead of print]85 104311

Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcome.

Andras T Meszaros, Julia Hofmann, Madita L Buch, Benno Cardini, Theresia Dunzendorfer-Matt, Florian Nardin, Michael J Blumer, Margot Fodor, Martin Hermann, Bettina Zelger, Giorgi Otarashvili, Melanie Schartner, Annemarie Weissenbacher, Rupert Oberhuber, Thomas Resch, Jakob Troppmair, Dietmar Fner, Heinz Zoller, Herbert Tilg, Erich Gnaiger, Theresa Hautz, Stefan Schneeberger.

  BACKGROUND: Reliable biomarkers for organ quality assessment during normothermic machine perfusion (NMP) are desired. ATP (adenosine triphosphate) production by oxidative phosphorylation plays a crucial role in the bioenergetic homeostasis of the liver. Thus, detailed analysis of the aerobic mitochondrial performance may serve as predictive tool towards the outcome after liver transplantation.METHODS: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh after reperfusion. Mitochondrial function and integrity were characterized by high-resolution respirometry (HRR), AMP, ADP, ATP and glutamate dehydrogenase analysis and correlated with the clinical outcome (L-GrAFT score). Real-time confocal microscopy was performed to assess tissue viability. Structural damage was investigated by histology, immunohistochemistry and transmission electron microscopy.
FINDINGS: A considerable variability in tissue viability and mitochondrial respiration between individual livers at the end of cold storage was observed. During NMP, mitochondrial respiration with succinate and tissue viability remained stable. In the multivariate analysis of the 35 transplanted livers (15 were discarded), area under the curve (AUC) of LEAK respiration, cytochrome c control efficiency (mitochondrial outer membrane damage), and efficacy of the mitochondrial ATP production during the first 6.ßh of NMP correlated with L-GrAFT.
INTERPRETATIONS: Bioenergetic competence during NMP plays a pivotal role in addition to tissue injury markers. The AUC for markers of outer mitochondrial membrane damage, ATP synthesis efficiency and dissipative respiration (LEAK) predict the clinical outcome upon liver transplantation.
FUNDING: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH.

Keywords:  High-resolution respirometry; Liver; Mitochondria; Normothermic machine perfusion; Transplantation

DOI:  https://doi.org/10.1016/j.ebiom.2022.104311
FEBS J. 2022 Nov;289(22): 6822-6831

Organelle homeostasis: from cellular mechanisms to disease.

Emma Burbridge, Colin Adrain.

  The major criterion that distinguishes eukaryotes from prokaryotes is the presence of organelles in the former. Organelles provide a compartment in which biochemical processes are corralled within bespoke biophysical conditions and act as storage depots, powerhouses, waste storage/recycling units and innate immune signalling hubs. A key challenge faced by organelles is to define, and then retain, their identity; this is mediated by complex proteostasis mechanisms including the import of an organelle-specific proteome, the exclusion of non-organellar proteins and the removal of misfolded proteins via dedicated quality control mechanisms. This Special Issue on Organelle Homeostasis provides an engaging, eclectic, yet integrative, perspective on organelle homeostasis in a range of organelles including those from the secretory and endocytic pathways, mitochondria, the autophagy-lysosomal pathway and the nucleus and its sub-compartments. Some lesser-known organelles including migrasomes (organelles that are released by migrating cells) and GOMED (a Golgi-specific form of autophagy) are also introduced. In the spirit of the principles of organelle biology, we hope you find the reviews in this Issue both encapsulating and captivating, and we thank the authors for their excellent contributions.

Keywords:  endoplasmic reticulum; mitochondria; nucleus; organelle homeostasis; quality control

DOI:  https://doi.org/10.1111/febs.16667