scholarly journals Drp-1-Dependent Mitochondrial Fragmentation Contributes to Cobalt Chloride-Induced Toxicity in Caenorhabditis elegans

2020 ◽  
Vol 177 (1) ◽  
pp. 158-167
Author(s):  
Fuli Zheng ◽  
Pan Chen ◽  
Huangyuan Li ◽  
Michael Aschner
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Cobalt Chloride ◽  
Mitochondrial Fission ◽  
Reactive Oxygen Species Generation ◽  
Related Factor ◽  
Mitochondrial Fragmentation ◽  
Glutathione S Transferase ◽  
Chain Reactions ◽  
Cobalt Exposure

Abstract Excess cobalt may lead to metallosis, characterized by sensorineural hearing loss, visual, and cognitive impairment, and peripheral neuropathy. In the present study, we sought to address the molecular mechanisms of cobalt-induced neurotoxicity, using Caenorhabditis elegans as an experimental model. Exposure to cobalt chloride for 2 h significantly decreased the survival rate and lifespan in nematodes. Cobalt chloride exposure led to increased oxidative stress and upregulation of glutathione S-transferase 4. Consistently, its upstream regulator skn-1, a mammalian homolog of the nuclear factor erythroid 2-related factor 2, was activated. Among the mRNAs examined by quantitative real-time polymerase chain reactions, apoptotic activator egl-1, proapoptotic gene ced-9, autophagic (bec-1 and lgg-1), and mitochondrial fission regulator drp-1 were significantly upregulated upon cobalt exposure, concomitant with mitochondrial fragmentation, as determined by confocal microscopy. Moreover, drp-1 inhibition suppressed the cobalt chloride-induced reactive oxygen species generation, growth defects, and reduced mitochondrial fragmentation. Our novel findings suggest that the acute toxicity of cobalt is mediated by mitochondrial fragmentation and drp-1 upregulation.

Abstract 568: Deletion of AMP-activated Protein Kinase-alpha Triggers Mitochondrial Fission and Endothelial Dysfunction

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Qqilong Wang ◽  
Zhonglin Xie ◽  
Huaiping Zhu ◽  
Ye Ding ◽  
Ming-Hui Zou
Keyword(s):  
Protein Kinase ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Chronic Administration ◽  
Mitochondrial Fragmentation ◽  
Aortic Endothelium ◽  
Amp Activated Protein Kinase

Introduction: AMP-activated protein kinase (AMPK) has been reported to regulate mitochondrial biogenesis, function, and turnover. However, the molecular mechanisms by which AMPK regulates mitochondrial dynamics remain poorly characterized. We hypothesized that AMPK deficiency regulates mitochondrial fission that will result in endothelial dysfunction. Methods/Results: Deletion of AMPKα2 resulted in defective autophagy, dynamin-related protein (Drp1) accumulation, and aberrant mitochondrial fragmentation in the aortic endothelium of mice. Furthermore, autophagy inhibition by chloroquine treatment or Atg7 small interfering RNA (siRNA) transfection upregulated Drp1 expression and triggered Drp1-mediated mitochondrial fragmentation. In contrast, autophagy activation by overexpression of Atg7 or chronic administration of rapamycin, the mammalian target of rapamycin kinase inhibitor, promoted Drp1 degradation and attenuated mitochondrial fission in AMPKα2 -/- mice, suggesting that defective autophagy contributes to enhanced Drp1 expression and mitochondrial fragmentation. Interesting, the genetic (Drp1 siRNA) or pharmacological (mdivi-1) inhibition of Drp1 ablated mitochondrial fragmentation in the mouse aortic endothelium and prevented the acetylcholine-induced relaxation of isolated mouse aortas from AMPKα2 -/- mice. This suggests that aberrant Drp1 is responsible for enhanced mitochondrial fission and endothelial dysfunction in AMPKα knockout mice. Conclusions: Our results show that AMPKα deletion promoted mitochondrial fission in vascular endothelial cells by inhibiting the autophagy-dependent degradation of Drp1.

scholarly journals Nicotinamide Treatment Facilitates Mitochondrial Fission through Drp1 Activation Mediated by SIRT1-Induced Changes in Cellular Levels of cAMP and Ca2+

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 612
Author(s):  
Seon Beom Song ◽  
Jin Sung Park ◽  
So Young Jang ◽  
Eun Seong Hwang
Keyword(s):  
Protein Kinase ◽  
Mitochondrial Fission ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Mitochondrial Fragmentation ◽  
Mitochondrial Quality Control ◽  
Induced Changes ◽  
Amp Activated Protein Kinase ◽  
Nicotinamide Treatment ◽  
Kinase A

Mitochondrial autophagy (or mitophagy) is essential for mitochondrial quality control, which is critical for cellular and organismal health by attenuating reactive oxygen species generation and maintaining bioenergy homeostasis. Previously, we showed that mitophagy is activated in human cells through SIRT1 activation upon treatment of nicotinamide (NAM). Further, mitochondria are maintained as short fragments in the treated cells. In the current study, molecular pathways for NAM-induced mitochondrial fragmentation were sought. NAM treatment induced mitochondrial fission, at least in part by activating dynamin-1-like protein (Drp1), and this was through attenuation of the inhibitory phosphorylation at serine 637 (S637) of Drp1. This Drp1 hypo-phosphorylation was attributed to SIRT1-mediated activation of AMP-activated protein kinase (AMPK), which in turn induced a decrease in cellular levels of cyclic AMP (cAMP) and protein kinase A (PKA) activity, a kinase targeting S637 of Drp1. Furthermore, in NAM-treated cells, cytosolic Ca2+ was highly maintained; and, as a consequence, activity of calcineurin, a Drp1-dephosphorylating phosphatase, is expected to be elevated. These results suggest that NAD+-mediated SIRT1 activation facilitates mitochondrial fission through activation of Drp1 by suppressing its phosphorylation and accelerating its dephosphorylation. Additionally, it is suggested that there is a cycle of mitochondrial fragmentation and cytosolic Ca2+-mediated Drp1 dephosphorylation that may drive sustained mitochondrial fragmentation.

scholarly journals Loss of AKAP1 triggers Drp1 dephosphorylation-mediated mitochondrial fission and loss in retinal ganglion cells

2019 ◽  
Author(s):  
Genea Edwards ◽  
Guy A. Perkins ◽  
Keun-Young Kim ◽  
YeEun Kong ◽  
Yonghoon Lee ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Mitochondrial Fission ◽  
Critical Role ◽  
Metabolic Stress ◽  
Retinal Ganglion ◽  
Mitochondrial Fragmentation ◽  
Akt Phosphorylation ◽  
Anchoring Protein

AbstractImpairment of mitochondrial structure and function is strongly linked to glaucoma pathogenesis. Despite the widely appreciated disease relevance of mitochondrial dysfunction and loss, the molecular mechanisms underlying mitochondrial fragmentation and metabolic stress in glaucoma are poorly understood. We demonstrate here that glaucomatous retinal ganglion cells (RGCs) show loss of A-kinase anchoring protein 1 (AKAP1), activation of calcineurin (CaN) and reduction of dynamin-related protein 1 (Drp1) phosphorylation at serine 637 (Ser637). These findings suggest that AKAP1-mediated phosphorylation of Drp1 at Ser637 has a critical role in RGC survival in glaucomatous neurodegeneration. Male mice lacking AKAP1 show increases of CaN and total Drp1 level, as well as a decrease of Drp1 phosphorylation at Ser637 in the retina. Ultrastructural analysis of mitochondria shows that loss of AKAP1 triggers mitochondrial fragmentation and loss, as well as mitophagosome formation in RGCs. Loss of AKAP1 deregulates oxidative phosphorylation (OXPHOS) complexes (Cxs) by increasing CxII and decreasing CxIII-V, leading to metabolic and oxidative stress. Also, loss of AKAP1 decreases Akt phosphorylation at Serine 473 (Ser473) and threonine 308 (Thr308) and activates the Bim/Bax signaling pathway in the retina. These results suggest that loss of AKAP1 has a critical role in RGC dysfunction by decreasing Drp1 phosphorylation at Ser637, deregulating OXPHOS, decreasing Akt phosphorylation at Ser473 and Thr308, and activating the Bim/Bax pathway in glaucomatous neurodegeneration. Thus, we propose that overexpression of AKAP1 or modulation of Drp1 phosphorylation at Ser637 are potential therapeutic strategies for neuroprotective intervention in glaucoma and other mitochondria-related optic neuropathies.

1182The novel mitophagic receptor protein bcl2-like protein 13: new insights for the molecular mechanisms of the pathogenesis of heart disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Murakawa ◽  
K Otsu
Keyword(s):  
Heart Disease ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Receptor Protein ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Fragmentation ◽  
Protein Database ◽  
L 13

Abstract Cardiac function highly depends on energy generated by mitochondria, which are injured by various stresses such as pressure overload or aging. Damaged mitochondria in failing hearts are removed by a mitochondria-specific autophagy, called mitophagy. Dysregulation of mitophagy is implicated in the pathogenesis of heart disease such as heart failure. Mitochondrial morphologies change continuously through actions of mitochondrial dynamics (fission and fusion) and mitophagy is closely associated with mitochondrial fission to make mitochondria engulfable size by autophagosomes. Atg32 is an essential protein for mitophagy in yeast. Some molecules have been reported to be involved in mitophagy, such as Parkin, FUNDC1 and Bnip3l. However, no Atg32 homologue has been identified in mammalian cells. We hypothesized that an unknown mammalian mitophagy receptor will share the molecular features with Atg32. By screening a public protein database for Atg32 homologues, we identified Bcl-2-like protein 13 (Bcl2-L-13). Initially, we examined the function of Bcl2-L-13 in cardiomyocytes from 1-day-old Wistar rats. Forty-eight hours after infection of cardiomyocytes with an adenoviral vector expressing Bcl2-L-13, mitochondrial fragmentation was induced. In contrast, knockdown of Bcl2-L-13 induced mitochondrial elongation. We carried out further investigation into functions of Bcl2-L-13 using cell lines. Bcl2-L-13 is localized at the mitochondrial outer membrane and bound to LC3 through the WXXI motif and induced mitochondrial fragmentation and mitophagy. In Bcl2-L-13, the BH domains are important for mitochondrial fragmentation, while the WXXI motif facilitates mitophagy. Bcl2-L-13 induces mitochondrial fragmentation in the absence of Drp1 which is the master regulator of mitochondrial fission, while it induces mitophagy in Parkin-deficient cells. Next, we investigated physiological function of Bcl2-L-13. Knockdown of Bcl2-L-13 attenuated CCCP (carbonyl cyanide m-chlorophenyl hydrazone)-induced fragmentation and mitophagy. CCCP upregulated the phosphorylation level of Bcl2-L-13 Ser272 and Ser272Ala mutant showed less ability for inducing mitophagy. Considering of these, phosphorylation of this protein may regulate its activity. Furthermore, Bcl2-L-13 completely restored mitophagy in atg32-deficient yeast, suggesting that Bcl2-L-13 is a mammalian functional homologue of Atg32. Our findings thus offer novel insights into molecular mechanisms of the pathogenesis of heart disease. Acknowledgement/Funding British Heart Foundation

scholarly journals GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Qiujie Wang ◽  
Cheng Bin ◽  
Qiang Xue ◽  
Qingzhu Gao ◽  
Ailong Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Hepatoma Cell ◽  
Redox Homeostasis ◽  
Lipid Peroxides ◽  
Tumor Growth Inhibition ◽  
Related Factor ◽  
Glutathione S Transferase ◽  
Hepatoma Cell Lines

AbstractIncreasing evidence supports that ferroptosis plays an important role in tumor growth inhibition. Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, has been shown to induce ferroptosis in hepatocellular carcinoma (HCC). However, some hepatoma cell lines are less sensitive to sorafenib-induced ferroptotic cell death. Glutathione S-transferase zeta 1 (GSTZ1), an enzyme in the catabolism of phenylalanine, suppresses the expression of the master regulator of cellular redox homeostasis nuclear factor erythroid 2-related factor 2 (NRF2). This study aimed to investigate the role and underlying molecular mechanisms of GSTZ1 in sorafenib-induced ferroptosis in HCC. GSTZ1 was significantly downregulated in sorafenib-resistant hepatoma cells. Mechanistically, GSTZ1 depletion enhanced the activation of the NRF2 pathway and increased the glutathione peroxidase 4 (GPX4) level, thereby suppressing sorafenib-induced ferroptosis. The combination of sorafenib and RSL3, a GPX4 inhibitor, significantly inhibited GSTZ1-deficient cell viability and promoted ferroptosis and increased ectopic iron and lipid peroxides. In vivo, the combination of sorafenib and RSL3 had a synergic therapeutic effect on HCC progression in Gstz1−/− mice. In conclusion, this finding demonstrates that GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells. Combination therapy of sorafenib and GPX4 inhibitor RSL3 may be a promising strategy in HCC treatment.

scholarly journals Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 195 ◽  
Author(s):  
Bong Jhun ◽  
Jin O-Uchi ◽  
Stephanie Adaniya ◽  
Michael Cypress ◽  
Yisang Yoon
Keyword(s):  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Mitochondrial Fission ◽  
Ros Generation ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Signaling Activation ◽  
And Function

Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca2+ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF.

scholarly journals Posttranslational modifications of mitochondrial fission and fusion proteins in cardiac physiology and pathophysiology

2019 ◽  
Vol 316 (5) ◽  
pp. C583-C604 ◽  
Author(s):  
Stephanie M. Adaniya ◽  
Jin O-Uchi ◽  
Michael W. Cypress ◽  
Yoichiro Kusakari ◽  
Bong Sook Jhun
Keyword(s):  
Posttranslational Modifications ◽  
Fusion Proteins ◽  
Molecular Mechanisms ◽  
Mitochondrial Fission ◽  
Cell Types ◽  
Mitochondrial Morphology ◽  
Mitochondrial Fragmentation ◽  
Physiological Relevance ◽  
Future Potential ◽  
The Stability

Mitochondrial fragmentation frequently occurs in chronic pathological conditions as seen in various human diseases. In fact, abnormal mitochondrial morphology and mitochondrial dysfunction are hallmarks of heart failure (HF) in both human patients and HF animal models. A link between mitochondrial fragmentation and cardiac pathologies has been widely proposed, but the physiological relevance of mitochondrial fission and fusion in the heart is still unclear. Recent studies have increasingly shown that posttranslational modifications (PTMs) of fission and fusion proteins are capable of directly modulating the stability, localization, and/or activity of these proteins. These PTMs include phosphorylation, acetylation, ubiquitination, conjugation of small ubiquitin-like modifier proteins, O-linked- N-acetyl-glucosamine glycosylation, and proteolysis. Thus, understanding the PTMs of fission and fusion proteins may allow us to understand the complexities that determine the balance of mitochondrial fission and fusion as well as mitochondrial function in various cell types and organs including cardiomyocytes and the heart. In this review, we summarize present knowledge regarding the function and regulation of mitochondrial fission and fusion in cardiomyocytes, specifically focusing on the PTMs of each mitochondrial fission/fusion protein. We also discuss the molecular mechanisms underlying abnormal mitochondrial morphology in HF and their contributions to the development of cardiac diseases, highlighting the crucial roles of PTMs of mitochondrial fission and fusion proteins. Finally, we discuss the future potential of manipulating PTMs of fission and fusion proteins as a therapeutic strategy for preventing and/or treating HF.

Abstract 283: SGK1-Dependent Sirt3 Phosphorylation Regulates Mitochondrial Dynamics

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Dallas Ellis ◽  
Takara Scott ◽  
Wei Zhong ◽  
Oguljahan Babayeva ◽  
Sharon C Francis
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Ectopic Expression ◽  
Mitochondrial Fragmentation ◽  
Proteomic Screen ◽  
Protein Levels ◽  
Stimulation Of

Mitochondrial dynamics (i.e. fusion and fission) is impaired in models of obesity and can result in target organ dysfunction. However, the mechanisms that regulate mitochondrial dynamics in the setting of obesity are not completely understood. The objectives of this study are to examine a role for and determine the molecular mechanisms of serum and glucocorticoid-inducible kinase 1 (SGK1) in obesity-related mitochondrial dynamics in the vasculature. We recently reported that aortic expression of SGK1 is elevated in a model of diet-induced obesity (DIO) in vivo and by resistin; a fat-derived adipokine, in human aortic smooth muscle cells (SMC) in vitro . To directly examine the effects of SMC-derived SGK1 on mitochondrial dynamics, wildtype and SMC-specific SGK1 knockout mice were subjected to DIO for eight weeks. Our results indicate that SMC-specific deletion of SGK1 induced a fused, elongated mitochondrial phenotype in aortic SMC in vivo and attenuated obesity-mediated arterial mitochondrial fragmentation suggesting a role for SGK1 in stimulation of mitochondrial fission. To determine the molecular mechanism for this effect, we performed a proteomic screen for novel SGK1 substrates and identified the mitochondrial deacetylase SIRT3 as a novel SGK1 target. Mass spectrometry indicates SGK1 phosphorylates SIRT3 on serine103. Increasing doses of resistin augmented SIRT3-S103 phosphorylation and caused a concomitant decrease in total SIRT3 in rat aortic SMC in vitro . To examine whether SGK1-dependent SIRT3 phosphorylation regulates the mitochondrial fission protein machinery; we evaluated total and activated levels of Drp1, the mitochondrial fission regulator, in response to ectopic expression of SIRT3 wildtype, phospho-memetic (S103D) and phospho-deficient (S103A) mutants. SIRT3-S103D increased total Drp1 and activated Drp1 protein levels an effect inhibited by SIRT3-S103A. These findings implicate elevated resistin observed during obesity in stimulation of SGK1 and subsequent phosphorylation of SIRT3 leading to activation of Drp1 and stimulation of arterial mitochondrial fragmentation.

scholarly journals Cigarette smoke-induced mitochondrial fragmentation and dysfunction in human airway smooth muscle

2014 ◽  
Vol 306 (9) ◽  
pp. L840-L854 ◽  
Author(s):  
Bharathi Aravamudan ◽  
Alexander Kiel ◽  
Michelle Freeman ◽  
Philippe Delmotte ◽  
Michael Thompson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Mitochondrial Fission ◽  
Related Factor ◽  
Mitochondrial Fragmentation ◽  
Human Airway Smooth Muscle ◽  
Human Airway ◽  
Mitochondrial Networks

The balance between mitochondrial fission and fusion is crucial for mitochondria to perform its normal cellular functions. We hypothesized that cigarette smoke (CS) disrupts this balance and enhances mitochondrial dysfunction in the airway. In nonasthmatic human airway smooth muscle (ASM) cells, CS extract (CSE) induced mitochondrial fragmentation and damages their networked morphology in a concentration-dependent fashion, via increased expression of mitochondrial fission protein dynamin-related protein 1 (Drp1) and decreased fusion protein mitofusin (Mfn) 2. CSE effects on Drp1 vs. Mfn2 and mitochondrial network morphology involved reactive oxygen species (ROS), activation of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), protein kinase C (PKC) and proteasome pathways, as well as transcriptional regulation via factors such as NF-κB and nuclear erythroid 2-related factor 2. Inhibiting Drp1 prevented CSE effects on mitochondrial networks and ROS generation, whereas blocking Mfn2 had the opposite, detrimental effect. In ASM from asmatic patients, mitochondria exhibited substantial morphological defects at baseline and showed increased Drp1 but decreased Mfn2 expression, with exacerbating effects of CSE. Overall, these results highlight the importance of mitochondrial networks and their regulation in the context of cellular changes induced by insults such as inflammation (as in asthma) or CS. Altered mitochondrial fission/fusion proteins have a further potential to influence parameters such as ROS and cell proliferation and apoptosis relevant to airway diseases.

scholarly journals Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein

2016 ◽  
Vol 27 (2) ◽  
pp. 349-359 ◽  
Author(s):  
Shan Xu ◽  
Edward Cherok ◽  
Shweta Das ◽  
Sunan Li ◽  
Brian A. Roelofs ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Mitochondrial Fission ◽  
E3 Ubiquitin Ligase ◽  
Negative Regulator ◽  
Mitochondrial Fragmentation ◽  
Cell Sensitivity ◽  
Response To Stress ◽  
Induced Apoptosis

Ubiquitin- and proteasome-dependent outer mitochondrial membrane (OMM)-associated degradation (OMMAD) is critical for mitochondrial and cellular homeostasis. However, the scope and molecular mechanisms of the OMMAD pathways are still not well understood. We report that the OMM-associated E3 ubiquitin ligase MARCH5 controls dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and cell sensitivity to stress-induced apoptosis. MARCH5 knockout selectively inhibited ubiquitination and proteasomal degradation of MiD49, a mitochondrial receptor of Drp1, and consequently led to mitochondrial fragmentation. Mitochondrial fragmentation in MARCH5−/− cells was not associated with inhibition of mitochondrial fusion or bioenergetic defects, supporting the possibility that MARCH5 is a negative regulator of mitochondrial fission. Both MARCH5 re-expression and MiD49 knockout in MARCH5−/− cells reversed mitochondrial fragmentation and reduced sensitivity to stress-induced apoptosis. These findings and data showing MARCH5-dependent degradation of MiD49 upon stress support the possibility that MARCH5 regulation of MiD49 is a novel mechanism controlling mitochondrial fission and, consequently, the cellular response to stress.

Sign in / Sign up

Export Citation Format

Share Document