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

“…Studies have shown that damaged proximal tubular cells produce matricellular thrombospondin 1 (THBS1) and High Mobility Group Box 1 (HMGB1), which can induce apoptosis; administration of THBS1 and HMGB1 inhibitors protected mice from kidney ischemia-reperfusion injury [129-131]. Previous studies have also suggested that an increase in platelet-derived factors can lead to an increase in GSK-3βSer9 phosphorylation levels and that Ser9 phosphorylation can inhibit apoptosis.…”

Section: Reduced Ischemia-reperfusion Injury Caused By Apoptosismentioning

confidence: 99%

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

Yiang

Liao

et al. 2018

Cell Physiol Biochem

889

663

View full text Add to dashboard Cite

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

show abstract

“…These proteins are resident OMM proteins and form rings and foci with a carboxy terminal domain and may be responsible for binding to inactive DRP1 dimers or inhibiting DRP1 GTPase activity [14,78,79]. MiD49 is a target of MARCH5 resulting in ubiquitylation and UPS dependent degradation [80]. MiD49 was found to be more abundant in MARCH5 depleted cells while the homolog, MiD51 was not changed.…”

Section: Outer Mitochondrial Membrane Fission and Fusionmentioning

confidence: 99%

Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein Turnover

Ali

McStay

2017

Preprint

View full text Add to dashboard Cite

The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as ATP synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by GTPases on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-translational proteolysis and/or turnover and this review will discuss these mechanisms required for correct mitochondrial network organization. IntroductionMitochondria are the power houses of every nucleated cell, generating chemical energy in the form of adenosine triphosphate (ATP) by the oxidative phosphorylation (OXPHOS) system. Mitochondria are also important for the normal functioning of the cells as they regulate several crucial activities like differentiation, cell cycle, intracellular signaling and cell death [1]. Mitochondria are unique because of their autonomous DNA (mtDNA), which encodes for proteins required for ATP synthesis. Therefore maintenance of mtDNA is important for normal mitochondrial function and for the diversity of mitochondrial genome [2]. Mitochondria form elongated tubules that continually divide and fuse to form a complex, interconnected and highly dynamic network inside of cells. These dynamics processes not only regulate mitochondrial function but also mitochondrial shape, content exchange and mitochondrial communication with the cytoskeleton [3]. Due to the involvement of mitochondria in a large spectrum of cellular functions, these organelles play a key role in mediating cellular homeostasis. As a result a healthy population of mitochondria is critical for cell survival.

show abstract

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

Cited by 118 publications

References 38 publications

Novel regulatory roles of Mff and Drp1 in E3 ubiquitin ligase MARCH5–dependent degradation of MiD49 and Mcl1 and control of mitochondrial dynamics

Novel regulatory roles of Mff and Drp1 in E3 ubiquitin ligase MARCH5–dependent degradation of MiD49 and Mcl1 and control of mitochondrial dynamics

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein Turnover

Contact Info

Product

Resources

About