Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cellular Senescence, Endosomal Sorting Complexes Required for Transport, F-Box Proteins, GTP Phosphohydrolases, Membrane Fusion, Membrane Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligase Complexes, Vacuoles
Mol. Biol. Cell
Date: Dec. 01, 2018
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