Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress
| Autor: | Adam Hughes, Austin R. Lever, Troy K. Coody, Daniel E. Gottschling, Jenna M. Goodrum |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Proteolysis Biosynthesis and Biodegradation Saccharomyces cerevisiae GTPase Vacuole Biology Membrane Fusion Mitochondrial Dynamics Cofactor GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Ubiquitin medicine Molecular Biology Cellular Senescence Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences SKP Cullin F-Box Protein Ligases Endosomal Sorting Complexes Required for Transport medicine.diagnostic_test F-Box Proteins Membrane Proteins Ubiquitin-Protein Ligase Complexes Signal transducing adaptor protein Articles Cell Biology Mitochondria Cell biology mitochondrial fusion Vacuoles biology.protein 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e19-02-0094 |
| Popis: | Mitochondrial decline is a hallmark of aging, and cells are equipped with many systems to regulate mitochondrial structure and function in response to stress and metabolic alterations. Here, using budding yeast, we identify a proteolytic pathway that contributes to alterations in mitochondrial structure in aged cells through control of the mitochondrial fusion GTPase Fzo1. We show that mitochondrial fragmentation in old cells correlates with reduced abundance of Fzo1, which is triggered by functional alterations in the vacuole, a known early event in aging. Fzo1 degradation is mediated by a proteolytic cascade consisting of the E3 ubiquitin ligases SCFMdm30and Rsp5, and the Cdc48 cofactor Doa1. Fzo1 proteolysis is activated by metabolic stress that arises from vacuole impairment, and loss of Fzo1 degradation severely impairs mitochondrial structure and function. Together, these studies identify a new mechanism for stress-responsive regulation of mitochondrial structure that is activated during cellular aging. |
| Databáze: | OpenAIRE |
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