Abstract:
: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 SCFMdm30 and 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.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Goodrum JM,Lever AR,Coody TK,Gottschling DE,Hughes ALdoi
10.1091/mbc.E19-02-0094subject
Has Abstractpub_date
2019-08-01 00:00:00pages
2141-2154issue
17eissn
1059-1524issn
1939-4586journal_volume
30pub_type
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