Selective sorting and destruction of mitochondrial membrane proteins in aged yeast.
Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells. Unlike many common mitochondrial degradation pathways, this system selectively removes a subset of membrane proteins from the mitochondrial inner and outer membranes, while leaving the remainder of the organelle intact. Selective removal of preexisting proteins is achieved by sorting into a mitochondrial-derived compartment, or MDC, followed by release through mitochondrial fission and elimination by autophagy. Formation of MDCs requires the import receptors Tom70/71, and failure to form these structures exacerbates preexisting mitochondrial dysfunction, suggesting that the MDC pathway provides protection to mitochondria in times of stress.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.|Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
Adam L
0000-0002-7095-3793
AL
Hughes
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
Casey E
CE
Hughes
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Kiersten A
KA
Henderson
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Nina
N
Yazvenko
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States.
Daniel E
0000-0002-7303-6552
DE
Gottschling
D000368:Aged; D006801:Humans; D051336:Mitochondrial Membranes / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*
D024101:Mitochondrial Proteins
MDC; S. cerevisiae; aging; autophagy; cell biology; lysosome; mitochondria; protein degradation; vacuole; yeast