bims-mitrat 2024-11-24 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2024–11–24
thirteen papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Nanotube-mediated mitochondrial transfer: power to the T cells!
Tak1 licenses mitochondrial transfer from astrocytes to POMC neurons to maintain glucose and cholesterol homeostasis.
Mitochondrial plasticity: An emergent concept in neuronal plasticity and memory.
Anti-aging effect of extracellular vesicles from mesenchymal stromal cells on senescence-induced chondrocytes in osteoarthritis.
Muscle fibroblasts and stem cells stimulate motor neurons in an age and exercise-dependent manner.
Voluntary wheel running decreases amyloidogenic pathway and rescues cognition and mitochondrial energy metabolism in middle-aged female 3xTg-AD mouse model of Alzheimer's disease.
Exercise Types: Physical Activity Mitigates Cardiac Aging and Enhances Mitochondrial Function via PKG-STAT3-Opa1 Axis.
NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.
Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria.
Muscle type-specific effects of bilateral abobotulinumtoxinA injection on muscle growth and contractile function in spastic mice.
Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation, and cell cycle progression.
SIRT1-dependent regulation of mitochondrial metabolism participates in miR-30a-5p-mediated cardiac remodeling post-myocardial infarction.
Hypothyroidism modulates mitochondrial dynamics and mitophagy in the heart of rats under fed and fasting conditions.

Trends Immunol. 2024 Nov 20. pii: S1471-4906(24)00272-2. [Epub ahead of print]

Nanotube-mediated mitochondrial transfer: power to the T cells!

Cosima T Baldari.

The success of T cell-based immunotherapies is limited by exhaustion, which is associated with mitochondrial dysfunction. Baldwin and colleagues show that bone marrow stromal cells (BMSCs) use nanotubes to transfer mitochondria to T cells, which increases mitochondria mass and fitness and boosts antitumor efficacy. The results pave the way to organelle-based therapies against cancer.

DOI: https://doi.org/10.1016/j.it.2024.11.001
Cell Rep. 2024 Nov 19. pii: S2211-1247(24)01334-2. [Epub ahead of print]43(12): 114983

Tak1 licenses mitochondrial transfer from astrocytes to POMC neurons to maintain glucose and cholesterol homeostasis.

Kaili Yin, Tingting Zhang, Xiyuan Lu, Qing Shen, Kaiyue Gu, Ying Huang, Chaonan Li, Jingyi Hou, Juxue Li, Guo Zhang.

  It remains incompletely understood how the astrocytes in the mediobasal hypothalamus (MBH) regulate systemic glucose and cholesterol metabolism. Here, we show that MBH astrocytic Tak1 (transforming growth factor β [TGF-β]-activated kinase 1) controls the metabolism of glucose and cholesterol. Tak1 is expressed in MBH astrocytes and activated after a short-term nutritional excess. In chow-fed mice, astrocytic deletion of Tak1 across the brain or its suppression in the MBH impairs glucose tolerance, reduces insulin sensitivity, and results in hypercholesterolemia. Astrocytic Tak1 activation in the MBH alleviates these symptoms in mice fed a high-fat diet (HFD). We show that astrocytic Tak1 modulates the activity of proopiomelanocortin (POMC) neurons and enables the transport of mitochondria from astrocytes to POMC neurons. In astrocytic Tak1 knockout mice, supplementation of CD38, a molecule that is crucial in mitochondrial transfer, restores glucose and cholesterol homeostasis. Overall, these findings highlight an important role of MBH astrocytic Tak1 in glucose and cholesterol metabolism.

Keywords:  CP: Metabolism; CP: Neuroscience; Tak1; astrocyte; glucose homeostasis; hypothalamus; mitochondrial transfer

DOI:  https://doi.org/10.1016/j.celrep.2024.114983
Neurobiol Dis. 2024 Nov 16. pii: S0969-9961(24)00342-5. [Epub ahead of print] 106740

Mitochondrial plasticity: An emergent concept in neuronal plasticity and memory.

Typhaine Comyn, Thomas Preat, Alice Pavlowsky, Pierre-Yves Plaçais.

  Mitochondria are classically viewed as 'on demand' energy suppliers to neurons in support of their activity. In order to adapt to a wide range of demands, mitochondria need to be highly dynamic and capable of adjusting their metabolic activity, shape, and localization. Although these plastic properties give them a central support role in basal neuronal physiology, recent lines of evidence point toward a role for mitochondria in the regulation of high-order cognitive functions such as memory formation. In this review, we discuss the interplay between mitochondrial function and neural plasticity in sustaining memory formation at the molecular and cellular levels. First, we explore the global significance of mitochondria in memory formation. Then, we will detail the memory-relevant cellular and molecular mechanisms of mitochondrial plasticity. Finally, we focus on those mitochondrial functions, including but not limited to ATP production, that give mitochondria their pivotal role in memory formation. Altogether, this review highlights the central role of mitochondrial structural and functional plasticity in supporting and regulating neuronal plasticity and memory.

Keywords:  Energy; Glia; Memory; Mitochondria dynamics; TCA cycle

DOI:  https://doi.org/10.1016/j.nbd.2024.106740
Aging (Albany NY). 2024 Nov 22. null

Anti-aging effect of extracellular vesicles from mesenchymal stromal cells on senescence-induced chondrocytes in osteoarthritis.

Jérémy Boulestreau, Marie Maumus, Giuliana Bertolino Minani, Christian Jorgensen, Danièle Noël.

  Age is the most important risk factor for degenerative diseases such as osteoarthritis (OA). It is associated with the accumulation of senescent cells in joint tissues that contribute to the pathogenesis of OA, in particular through the release of senescence-associated secretory phenotype (SASP) factors. Mesenchymal stromal cells (MSCs) and their derived extracellular vesicles (EVs) are promising treatments for OA. However, the senoprotective effects of MSC-derived EVs in OA have been poorly investigated. Here, we used EVs from human adipose tissue-derived MSCs (ASC-EVs) in two models of inflammaging (IL1β)- and DNA damage (etoposide)-induced senescence in OA chondrocytes. We showed that the addition of ASC-EVs was effective in reducing senescence parameters, including the number of SA-β-Gal-positive cells, the accumulation of γH2AX foci in nuclei and the secretion of SASP factors. In addition, ASC-EVs demonstrated therapeutic efficacy when injected into a murine model of OA. Several markers of senescence, inflammation and oxidative stress were decreased shortly after injection likely explaining the therapeutic efficacy. In conclusion, ASC-EVs exert a senoprotective function both in vitro, in two models of induced senescence in OA chondrocytes and, in vivo, in the murine model of collagenase-induced OA.

Keywords:  aging; extracellular vesicle; mesenchymal stromal cell; osteoarthritis; regenerative medicine; senescence

DOI:  https://doi.org/10.18632/aging.206158
Aging Cell. 2024 Nov 18. e14413

Muscle fibroblasts and stem cells stimulate motor neurons in an age and exercise-dependent manner.

Casper Soendenbroe, Peter Schjerling, Cecilie J L Bechshøft, Rene B Svensson, Laurent Schaeffer, Michael Kjaer, Bénédicte Chazaud, Arnaud Jacquier, Abigail L Mackey.

  Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise.

Keywords:  aging; neural plasticity; neurodegeneration; sarcopenia; satellite stem cell; skeletal muscle; training

DOI:  https://doi.org/10.1111/acel.14413
J Alzheimers Dis. 2024 Nov;102(2): 424-436

Voluntary wheel running decreases amyloidogenic pathway and rescues cognition and mitochondrial energy metabolism in middle-aged female 3xTg-AD mouse model of Alzheimer's disease.

Jonathas Rodrigo Dos Santos, Carlos Henrique Rocha Catalão, Anderson Vulczak, Ana Elisa Caleiro Seixas Azzolini, Luciane Carla Alberici.

   BACKGROUND: Evidence supports the neuroprotective effects of physical activity, either in experimental animal models or humans. However, the biological mechanisms by which physical exercise modulates dementia and Alzheimer's disease (AD) progression are still unclear.
OBJECTIVE: This study investigated whether long-term (6 months) of voluntary wheel running induces neuroprotective effects in the pathogenesis of AD in middle-aged (8 months) female mice, focusing on energy metabolism.
METHODS: A genetic mice model of AD (3xTg-AD) that performed wheel running presented changes in body metabolism and muscle oxidative profile, as well as restored discriminative and non-associative retention memories, evaluated by novel object recognition and open field tasks, respectively.
RESULTS: In the hippocampus, these mice exhibited reduced levels of amyloidogenic AβPPβ fragment, phospho-Tau protein and phospho-Akt (activated form), without changes in phospho-AMPK (activated form). In addition, hippocampal mitochondria presented a restored respiratory function, characterized by lower coupling degree and weak contribution from complex I found in 3xTg-AD mice.
CONCLUSIONS: The results demonstrated that voluntary exercise improves cognitive parameters and biochemical hallmarks of AD, modulates Akt activation and enhances mitochondrial energy metabolism in hippocampus of middle-aged 3xTg-AD female mice, thereby reinforcing the neuroprotective role of physical exercise and the involvement of mitochondria in the etiology of the AD.

Keywords:  Alzheimer's disease; AβPP; mitochondrial energy metabolism; voluntary wheel running

DOI:  https://doi.org/10.1177/13872877241289388
Aging Dis. 2024 Nov 19.

Exercise Types: Physical Activity Mitigates Cardiac Aging and Enhances Mitochondrial Function via PKG-STAT3-Opa1 Axis.

Reka Szekeres, Daniel Priksz, Mariann Bombicz, Beata Pelles-Tasko, Anna Szilagyi, Brigitta Bernat, Aniko Posa, Balazs Varga, Rudolf Gesztelyi, Sandor Somodi, Zoltan Szabo, Zoltan Szilvassy, Bela Juhasz.

Although age-related deterioration of the cardiac function is a well-studied area of research, the interventions and their molecular pathways have not yet been fully identified. Since physical activity is a powerful preventive measure against cardiac aging, our study compared the effects of long-term voluntary and forced physical activity with a sedentary group, utilizing an aging rat model characterized by mitochondrial dysfunction that contributes to age-related cardiovascular diseases. Four experimental groups were created: (I) young controls (12-week-old); (II) 18-month-old aged sedentary rats; (III) aged group with free access to running wheels for 6 months; (IV) aged rats subjected to forced physical activity for 6 months. At the endpoint of the study, the aged animals were two years old. The aged sedentary rats exhibited increased Tei-index, LA/Ao and E/e' ratios as well as decreased e'/a' ratio and lengthened DecT and IVRT, higher perivascular fibrosis ratio and reduced myocardial PKG, STAT3 and Opa1 protein expression, along with decreased ATP synthase (ATPS) activity in comparison to the young controls. In terms of echocardiographic parameters and perivascular fibrosis, the forced running provided more substantial benefits than the voluntary activity demonstrated by decreased Tei-index, E/e' ratio, increased e'/a' ratio and reduced DecT and IVRT. Forced exercise was strongly associated with elevated myocardial expression of PKG, STAT3 and Opa1 proteins and, moreover, the ATPS activity was restored only in the forced running rats. In conclusion, forced but not voluntary exercise has significant protective effects on age-associated diastolic dysfunction by upregulating PKG-STAT3-Opa1 axis and thereby enhancing ATPS activity.

DOI: https://doi.org/10.14336/AD.2024.0959
Nat Commun. 2024 Nov 16. 15(1): 9945

NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.

Jie Wang, Rui Zhao, Sha Xu, Xiang-Yu Zhou, Ke Cai, Yu-Ling Chen, Ze-Yu Zhou, Xin Sun, Yan Shi, Feng Wang, Yong-Hao Gui, Hui Tao, Jian-Yuan Zhao.

Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism. Targeting NICD1 to mitochondria induces more EndMT compared with wild-type NICD1, and small molecule activation of PDH during pregnancy improves the phenotype in a mouse model of congenital heart defect. A NOTCH1 mutation observed in non-syndromic tetralogy of Fallot patients decreases NICD1 mitochondrial localization and subsequent PDH activity in heart tissues. Altogether, our findings demonstrate NICD1 enrichment in mitochondria of the developing mouse heart, which induces EndMT by activating PDH and subsequently improving mitochondrial metabolism.

DOI: https://doi.org/10.1038/s41467-024-54407-7
Mol Med. 2024 Nov 19. 30(1): 221

Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria.

Meagan S Kingren, Alexander R Keeble, Alyson M Galvan-Lara, Jodi M Ogle, Zoltán Ungvári, Daret K St Clair, Timothy A Butterfield, Allison M Owen, Christopher S Fry, Samir P Patel, Hiroshi Saito.

   BACKGROUND: Sepsis, mainly caused by bacterial infections, is the leading cause of in-patient hospitalizations. After discharge, most sepsis survivors suffer from long-term medical complications, particularly chronic skeletal muscle weakness. To investigate this medical condition in detail, we previously developed a murine severe sepsis-survival model that exhibits long-term post-sepsis skeletal muscle weakness. While mitochondrial abnormalities were present in the skeletal muscle of the sepsis surviving mice, the relationship between abnormal mitochondria and muscle weakness remained unclear. Herein, we aimed to investigate whether mitochondrial abnormalities have a causal role in chronic post-sepsis muscle weakness and could thereby serve as a therapeutic target.
METHODS: Experimental polymicrobial abdominal sepsis was induced in 16-18 months old male and female mice using cecal slurry injection with subsequent antibiotic and fluid resuscitation. To evaluate the pathological roles of mitochondrial abnormalities in post-sepsis skeletal muscle weakness, we utilized a transgenic mouse strain overexpressing the mitochondria-specific antioxidant enzyme manganese superoxide dismutase (MnSOD). Following sepsis development in C57BL/6 mice, we evaluated the effect of the mitochondria-targeting synthetic tetrapeptide SS-31 in protecting mitochondria from sepsis-induced damage and preventing skeletal muscle weakness development. In vivo and in vitro techniques were leveraged to assess muscle function at multiple timepoints throughout sepsis development and resolution. Histological and biochemical analyses including bulk mRNA sequencing were used to detect molecular changes in the muscle during and after sepsis RESULTS: Our time course study revealed that post sepsis skeletal muscle weakness develops progressively after the resolution of acute sepsis and in parallel with the accumulation of mitochondrial abnormalities and changes in the mitochondria-related gene expression profile. Transgenic mice overexpressing MnSOD were protected from mitochondrial abnormalities and muscle weakness following sepsis. Further, pharmacological protection of mitochondria utilizing SS-31 during sepsis effectively prevented the later development of muscle weakness.
CONCLUSIONS: Our study revealed that the accumulation of mitochondrial abnormalities is the major cause of post-sepsis skeletal muscle weakness. Pharmacological protection of mitochondria during acute sepsis is a potential clinical treatment strategy to prevent post-sepsis muscle weakness.

Keywords:  Critical care illness; Mitochondrial myopathy; Muscle weakness; Post-sepsis syndrome

DOI:  https://doi.org/10.1186/s10020-024-00982-w
FASEB J. 2024 Nov 30. 38(22): e70141

Muscle type-specific effects of bilateral abobotulinumtoxinA injection on muscle growth and contractile function in spastic mice.

Cintia Rivares, Alban Vignaud, Wendy Noort, Guus Baan, Bastijn Koopmans, Maarten Loos, Rob C I Wüst, Mikhail Kalinichev, Richard T Jaspers.

  Intramuscular injection of botulinum neurotoxin type A (BoNT-A) is commonly used to improve or maintain the joint range of motion in young children with spasticity. However, the effectiveness of BoNT-A treatment is variable and movement limitations are recurrent. Here we show long-term effects of a single, bilateral abobotulinumtoxinA (aboBoNT-A) injection in the gastrocnemius medialis and soleus muscles of wild-type and spastic (B6.Cg-Glrbspa/J with a mutation in the glycine receptor) mice at a young age (6-7 days). Specifically, we evaluated the impact of aboBoNT-A-A on gait, physical performance, and spontaneous physical behavior, as well as on contractile force characteristics, morphology, and histological phenotype of soleus and gastrocnemius muscles by comparing their results to those of saline-injected controls up to 9 weeks after the injection. The detailed time course of the study specifies the timing of the aboBoNT-A injection at 1 week, the period of behavioral studies from 4-9 weeks, and the age of the mice (10 weeks) at the time of contractile force characteristics and histology assessments. In spastic mice, aboBoNT-A injection had a minor and very specific effect on physical performance, by only modestly increasing stride length as a function of age. aboBoNT-A injection caused a reduction in the force-generating capacity and a slightly smaller physiological cross-sectional area in gastrocnemius medialis, but not in soleus. Reduced physiological cross-sectional area in aboBoNT-A-injected muscles was due to a lower number of muscle fibers, rather than reduced muscle fiber cross-sectional area. The percentage of slow-type muscle fibers and mitochondrial succinate dehydrogenase activity were increased, which was associated with an improved muscle endurance capacity. In conclusion, aboBoNT-A injection reduced the number of muscle fibers, causing muscle hypertrophy in remaining fibers and a shift towards more oxidative fibers, resulting in an improved endurance capacity and gait. This study proposed potential cellular mechanisms for the therapeutic efficacy of aboBoNT-A in spasticity.

Keywords:  chemical denervation; gait; muscle endurance; muscle fiber typing; muscle oxidative capacity; physiological cross‐sectional area; plantar flexor muscles; sarcomeres

DOI:  https://doi.org/10.1096/fj.202302258R
bioRxiv. 2024 Nov 06. pii: 2024.11.06.622334. [Epub ahead of print]

Miro1 expression alters global gene expression, ERK1/2 phosphorylation, oxidation, and cell cycle progression.

Nathaniel Shannon, Cory Raymond, Chloe Palmer, David Seward, Brian Cunniff.

Subcellular mitochondrial positioning in cells is necessary for localized energy and signaling requirements. Mitochondria are strategically trafficked throughout the cytoplasm via the actin cytoskeleton, microtubule motor proteins, and adaptor proteins. Miro1, an outer mitochondrial membrane adaptor protein, is necessary for attachment of mitochondria to microtubule motor proteins for trafficking. Previous work showed when Miro1 is deleted (Miro1 -/- ) from mouse embryonic fibroblasts (MEFs), the mitochondria become sequestered to the perinuclear space, disrupting subcellular energy and reactive oxygen species gradients. Here, we show that Miro1 -/- MEFs grow slower compared to Miro1 +/+ and Miro1 -/- MEFs stably re-expressing the Myc-Miro1 plasmid. Miro1 -/- MEFs have a have a cell cycle defect with decreased percentage of cells in G1 and increased cells in the S phase of the cell cycle. We conducted the first ever RNA sequencing experiment dependent upon Miro1 expression and found differential expression in cell proliferation and migration genes upon deletion of Miro1, including the MAP Kinase signaling pathway. We find that ERK1/2 phosphorylation is elevated both spatially (cytoplasm and nucleus) and temporally following serum stimulation in Miro1 -/- MEFs. We investigated the expression levels and oxidation of the Dual Specificity Phosphatases (DUSP1-6), ERK1/2 target phosphatases. We found no differences in DUSP1-6 expression and oxidation under asynchronous and synchronized cells. Lastly, we evaluated the oxidation status of ERK1/2 and found an increase in ERK1/2 oxidation in the Miro1 -/- MEFs compared to Miro1 +/+ and Myc-Miro1. These data highlight transcriptional control based off Miro1 expression and demonstrate the highly dynamic regulation of ERK1/2 upon deletion of Miro1 that may support the observed cell cycle and proliferation defects.

DOI: https://doi.org/10.1101/2024.11.06.622334
Free Radic Biol Med. 2024 Nov 16. pii: S0891-5849(24)01063-3. [Epub ahead of print]226 117-128

SIRT1-dependent regulation of mitochondrial metabolism participates in miR-30a-5p-mediated cardiac remodeling post-myocardial infarction.

Chan Wu, Yi-Xiang Hong, Xiao-Cheng Zhang, Jing-Zhou Li, Yu-Ting Li, Jun Xie, Rui-Ying Wang, Yan Wang, Gang Li.

  Myocardial infarction-triggered myocardial remodeling is fatal for therapies. The miR-30 family is an essential component of several physiological and pathological processes. Previous studies have proved that the miR-30 family may contribute to regulating myocardial infarction. This study aimed to demonstrate that the combination of miR-30a-5p and mitochondrial metabolism recapitulates the critical features for remodeling post-myocardial infarction. Using gain- and loss-of-function of miR-30a-5p in mice, we found miR-30a-5p is highly expressed in the heart and is reduced in infarcted hearts. Further evidence showed that miR-30a-5p acts as a protective molecule to maintain myocardial remodeling, fibrosis, and mitochondrial structure. Mitochondrial function, ATP production, and mitochondrial respiratory chain proteins were positively regulated by miR-30a-5p. Mechanistically, alterations in these properties depend on SIRT1, which modulates miR-30a-5p-regulated mitochondrial metabolism. Remarkably, reactivation of SIRT1 prevented miR-30a-5p deficiency-aggravated myocardial infarction-induced myocardial remodeling. These data identified miR-30a-5p as a critical modulator of mitochondrial function in cardiomyocytes and revealed that the miR-30a-5p-SIRT1-mitochondria network is essential for myocardial infarction-induced cardiac remodeling.

Keywords:  Mitochondrial metabolism; Myocardial infarction; SIRT1; miR-30a-5p

DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.11.030
Life Sci. 2024 Nov 15. pii: S0024-3205(24)00844-0. [Epub ahead of print]359 123254

Hypothyroidism modulates mitochondrial dynamics and mitophagy in the heart of rats under fed and fasting conditions.

Juliana Santos Romão, Jessika Geisebel Oliveira Neto, Cherley Borba Vieira Andrade, Jorge José Carvalho, Carmen Cabanelas Pazos-Moura, Karen Jesus Oliveira.

   AIMS: Investigate the impact of hypothyroidism on mitochondrial dynamics and mitophagy in the heart under fed and fasting conditions.
METHODS: Hypothyroidism was induced in male Wistar rats with methimazole (0.03 %) for 21 days. Half of the euthyroid and hypothyroid groups underwent a 48-h fasting. Mitochondrial number and ultrastructure were evaluated by transmission electron microscopy. Fusion, fission, mitophagy, oxidative stress, and mitochondrial oxidative phosphorylation system (OXPHOS) components were analyzed by Western Blot and qPCR.
RESULTS: Hypothyroidism increased DRP1 activation and the p-DRP1/OPA1 ratio, indicating a shift toward mitochondrial fission over fusion. Under fasting, hypothyroidism prevented the increases in mitochondrial size, elongation, OPA1, and OXPHOS seen in euthyroid fasted rats. Hypothyroidism also raised 4-HNE content, an oxidative stress product, increased mitochondrial injury, and exacerbated fasting-related mitochondrial damage. This was accompanied by elevated Parkin levels in both fed and fasted hypothyroid groups, but without changes in PINK1 levels or Parkin activation. While fasting upregulated Bnip3l and Map1lc3b expression in euthyroid rats, hypothyroidism suppressed this response, though it did not prevent fasting-induced Bnip3 increases.
CONCLUSIONS: Hypothyroidism increases the activation of mitochondrial fission machinery and oxidative stress, and induces mitochondrial damage without activation of mitophagy proteins, suggesting disrupted mitophagy signaling. It also interferes with fasting-induced mitochondrial dynamics adaptations, highlighting the essential role of thyroid hormones in metabolic adaptation to fasting.

Keywords:  Autophagy; Fission; Fusion; Mitochondria; Thyroid hormone

DOI:  https://doi.org/10.1016/j.lfs.2024.123254