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The mechanism of the Ant1-induced pathologies is highly debated. Here we show that equivalent mutations in the yeast Aac2 protein cause protein misfolding. Misfolded Aac2 drastically affects the assembly and stability of multiple protein complexes in the membrane, which ultimately inhibits cell growth. Despite causing similar proteostatic damages, the adPEO- but not the cardiomyopathy\/myopathy-type Aac2 proteins form large aggregates. The data suggest that the Ant1-induced diseases belong to protein misfolding disorders. Protein homeostasis is subtly maintained on the mitochondrial inner membrane and can be derailed by the misfolding of one single protein with or without aggregate formation. This finding could have broad implications for understanding other dominant diseases (e.g., retinitis pigmentosa) caused by missense mutations in membrane proteins.<\/jats:p>","DOI":"10.1091\/mbc.e15-01-0030","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T13:19:27Z","timestamp":1427980767000},"page":"1985-1994","source":"Crossref","is-referenced-by-count":25,"title":["Misfolding of mutant adenine nucleotide translocase in yeast supports a novel mechanism of Ant1-induced muscle diseases"],"prefix":"10.1091","volume":"26","author":[{"given":"Yaxin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, State University of New York Upstate 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