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Free keywords:
UBIQUITIN-PROTEASOME SYSTEM; ALPHA-SYNUCLEIN AGGREGATION;
SACCHAROMYCES-CEREVISIAE; HEAT-SHOCK; QUALITY-CONTROL; SUMO
MODIFICATION; STRESS-RESPONSE; ALCOHOL-DEHYDROGENASE; MISFOLDED
PROTEINS; PRECURSOR PROTEINBiochemistry & Molecular Biology; 70-kilodalton heat shock protein (HSP70); mitochondria; proteasome;
proteostasis; small ubiquitin-like modifier (SUMO); mitochondrial
proteins; protein quality control; SUMOylation;
Abstract:
Modification by the ubiquitin-like protein SUMO affects hundreds of cellular substrate proteins and regulates a wide variety of physiological processes. While the SUMO system appears to predominantly target nuclear proteins and, to a lesser extent, cytosolic proteins, hardly anything is known about the SUMOylation of proteins targeted to membrane-enclosed organelles. Here, we identify a large set of structurally and functionally unrelated mitochondrial proteins as substrates of the SUMO pathway in yeast. We show that SUMO modification of mitochondrial proteins does not rely on mitochondrial targeting and, in fact, is strongly enhanced upon import failure, consistent with the modification occurring in the cytosol. Moreover, SUMOylated forms of mitochondrial proteins particularly accumulate in HSP70- and proteasome-deficient cells, suggesting that SUMOylation participates in cellular protein quality control. We therefore propose that SUMO serves as a mark for nonfunctional mitochondrial proteins, which only sporadically arise in unstressed cells but strongly accumulate upon defective mitochondrial import and impaired proteostasis. Overall, our findings provide support for a role of SUMO in the cytosolic response to aberrant proteins.
