title: Mitochondrial release of the NADH dehydrogenase Ndi1 induces apoptosis in yeast.
abstract: Saccharomyces cerevisiae NDI1 codes for the internal mitochondrial ubiquinone oxidoreductase, which transfers electrons from NADH to ubiquinone in the respiratory chain. Previously we found that Ndi1 is a yeast homologue of the protein apoptosis-inducing factor-homologous mitochondrion-associated inducer of death and displays potent proapoptotic activity. Here we show that S. cerevisiae NDI1 is involved in apoptosis induced by various stimuli tested, including H(2)O(2), Mn, and acetate acid, independent of Z-VAD-fmk (a caspase inhibitor) inhibition. Although Ndi1 also participates in respiration, its proapoptotic property is separable from the ubiquinone oxidoreductase activity. During apoptosis, the N-terminal of Ndi1 is cleaved off in the mitochondria, and this activated form then escapes out to execute its apoptotic function. The N-terminal cleavage appears to be essential for the manifestation of the full apoptotic activity, as the uncleaved form of Ndi1 exhibits much less growth-inhibitory activity. Our results thus indicate an important role of Ndi1 in the switch of life and death fates in yeast: during normal growth, Ndi1 assimilates electrons to the electron transport chain and initiates the respiration process to make ATP, whereas under stresses, it cleaves the toxicity-sequestering N-terminal cap, is released from the mitochondria, and becomes a cell killer.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Cui
authors.forename: Shanke
authors.initials: S
authors.lastname: Zhao
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wu
authors.forename: Pinghua
authors.initials: P
authors.lastname: Dai
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D000085:Acetates; C493237:Ndi1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008345:Manganese; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D042967:Electron Transport Complex I