MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation
Autor: | Zhenya Hong, Jane E. Craig, Taosheng Chen, Lily Jun Shen Huang, Wei Zhuang, Gamze B. Bulut, Sadie Miki Sakurada, Jonathan Low, Malia B. Potts, Jamshid Temirov, Joseph N. Miller, Raju R. Rayavarapu, Shondra M. Pruett-Miller |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Mitochondrial Turnover Immunology Regulator Mitochondrial Degradation Mitochondrion lcsh:RC254-282 Article 03 medical and health sciences Cellular and Molecular Neuroscience Stress signalling 0302 clinical medicine Mitophagy lcsh:QH573-671 lcsh:Cytology Chemistry Autophagy Cell Biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology 030104 developmental biology Mitochondrial biogenesis 030220 oncology & carcinogenesis Homeostasis |
Zdroj: | Cell Death Discovery Cell Death Discovery, Vol 6, Iss 1, Pp 1-13 (2020) |
ISSN: | 2058-7716 |
Popis: | Mitochondria are vital organelles that coordinate cellular energy homeostasis and have important roles in cell death. Therefore, the removal of damaged or excessive mitochondria is critical for maintaining proper cellular function. The PINK1-Parkin pathway removes acutely damaged mitochondria through a well-characterized mitophagy pathway, but basal mitochondrial turnover occurs via distinct and less well-understood mechanisms. Here we report that the MEKK3-MEK5-ERK5 kinase cascade is required for mitochondrial degradation in the absence of exogenous damage. We demonstrate that genetic or pharmacological inhibition of the MEKK3-MEK5-ERK5 pathway increases mitochondrial content by reducing lysosome-mediated degradation of mitochondria under basal conditions. We show that the MEKK3-MEK5-ERK5 pathway plays a selective role in basal mitochondrial degradation but is not required for non-selective bulk autophagy, damage-induced mitophagy, or restraint of mitochondrial biogenesis. This illuminates the MEKK3-MEK5-ERK5 pathway as a positive regulator of mitochondrial degradation that acts independently of exogenous mitochondrial stressors. |
Databáze: | OpenAIRE |
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