Open AccessRsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress
Author(s) -
Jenna M. Goodrum,
Austin R. Lever,
Troy K. Coody,
Daniel E. Gottschling,
Adam L. Hughes
Publication year - 2019
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e19-02-0094
Subject(s) - biology , microbiology and biotechnology , mitochondrion , mitochondrial fusion , vacuole , autophagy , proteolysis , fragmentation (computing) , mitochondrial dna , biochemistry , apoptosis , enzyme , cytoplasm , gene , ecology
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 SCF Mdm30 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.