Yeast Mitochondrial Protein鈥揚rotein Interactions Reveal Diverse Complexes and Disease-Relevant Functional Relationships
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- 作者：Ke Jin ; Gabriel Musso ; James Vlasblom ; Matthew Jessulat ; Viktor Deineko ; Jacopo Negroni ; Roberto Mosca ; Ramy Malty ; Diem-Hang Nguyen-Tran ; Hiroyuki Aoki ; Zoran Minic ; Tanya Freywald ; Sadhna Phanse ; Qian Xiang ; Andrew Freywald ; Patrick Aloy ; Zhaolei Zhang ; Mohan Babu
- 刊名：Journal of Proteome Research
- 出版年：2015
- 出版时间：February 6, 2015
- 年：2015
- 卷：14
- 期：2
- 页码：1220-1237
- 全文大小：1031K
- ISSN：1535-3907
文摘
Although detailed, focused, and mechanistic analyses of associations among mitochondrial proteins (MPs) have identified their importance in varied biological processes, a systematic understanding of how MPs function in concert both with one another and with extra-mitochondrial proteins remains incomplete. Consequently, many questions regarding the role of mitochondrial dysfunction in the development of human disease remain unanswered. To address this, we compiled all existing mitochondrial physical interaction data for over 1200 experimentally defined yeast MPs and, through bioinformatic analysis, identified hundreds of heteromeric MP complexes having extensive associations both within and outside the mitochondria. We provide support for these complexes through structure prediction analysis, morphological comparisons of deletion strains, and protein co-immunoprecipitation. The integration of these MP complexes with reported genetic interaction data reveals substantial crosstalk between MPs and non-MPs and identifies novel factors in endoplasmic reticulum鈥搈itochondrial organization, membrane structure, and mitochondrial lipid homeostasis. More than one-third of these MP complexes are conserved in humans, with many containing members linked to clinical pathologies, enabling us to identify genes with putative disease function through guilt-by-association. Although still remaining incomplete, existing mitochondrial interaction data suggests that the relevant molecular machinery is modular, yet highly integrated with non-mitochondrial processes.