Mitochondrial Ubiquitin Ligase MITOL/MARCH5
Regulation of Mitochondrial Morphology by MITOL
Degradation of Misfolded Proteins by MITOL
MITOL Protects Mitochondria Against Nitrosative Stress
Role of MITOL in Interaction of Mitochondria and Endoplasmic Reticulum
Role of MITOL in the Immune System
Mitochondria serve as a platform for antiviral signal transduction. Toll-like receptors are a family of transmembrane receptors that play a key role in innate immunity. TANK (also called I-TRAF) is a negative regulator of Toll-like receptor-mediated induction of proinflammatory cytokines. MITOL mediates the addition of lysine-63-linked polyubiquitin chains to several lysine residues in TANK and impairs the ability of TANK to inhibit TRAF6. Thus, MITOL positively regulates TLR7 signaling via TANK inhibition (Shi et al. 2011) (PMID: 21625535).
Role of MITOL in Maintaining the Stemness of Embryonic Stem Cells
Mitochondrial morphology is strictly regulated by a balance between fission and fusion. Disruption in this balance induces mitochondrial impairment, resulting in a variety of diseases including neurodegenerative disorders, heart failure, and aging-associated diseases. The mitochondrial ubiquitin ligase MITOL plays an important role in the regulation of mitochondrial dynamics via Drp1 and Mfn2 (Nagashima et al. 2014), suggesting that MITOL dysfunction causes various diseases. Furthermore, MITOL has multiple functions in mitochondria, including in mitochondrial quality control via misfolded protein degradation, nitrosative stress response, signaling in innate immunity, and embryonic development. Further studies on MITOL should deepen our understanding of various diseases including aging-associated diseases.
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