Selective sorting and destruction of mitochondrial membrane proteins in aged yeast

• Published in: eLife Vol. 5
• Main Authors: Hughes, Adam L, Hughes, Casey E, Henderson, Kiersten A, Yazvenko, Nina, Gottschling, Daniel E
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 20-04-2016; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Age; Aged; Aging; Autophagy; Biodegradation; Cameras; Cell Biology; Homeostasis; Humans; Kinases; lysosome; Membrane proteins; Metabolism; Microscopy; Mitochondria; Mitochondrial Membranes - chemistry; Mitochondrial Proteins - metabolism; Mutation; Outer membranes; Phagocytosis; Physiological aspects; protein degradation; Protein Transport; Proteins; Proteolysis; Proteomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - physiology; yeast; Yeast fungi; autophagy; cell biology; vacuole; mitochondria; aging; MDC; lysosome; protein degradation; yeast; S. cerevisiae
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.13943

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.