Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging.
Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarified. Here, we show that overexpression of yeast AMID homologue internal NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause apoptosis-like cell death, and this effect can be repressed by increased respiration on glucose-limited media. This result indicates that the regulatory network of energy metabolism, in particular the cross-talk between mitochondria and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The apoptotic effect of NDI1 overexpression is associated with increased production of reactive oxygen species (ROS) in mitochondria. In addition, NDI1 overexpression in sod2 background causes cell lethality in both fermentable and semifermentable media. Interruption of certain components in the electron transport chain can suppress the growth inhibition from Ndi1p overexpression. We finally show that disruption of NDI1 or NDE1 decreases ROS production and elongates the chronological life span of yeast, accompanied by the loss of survival fitness. Implication of these findings for Ndi1p-induced apoptosis is discussed.
Li
Wei
W
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Sun
Libo
L
Liang
Qiuli
Q
Wang
Juan
J
Mo
Weike
W
Zhou
Bing
B
D017209:Apoptosis; D004579:Electron Transport; D042967:Electron Transport Complex I; D017353:Gene Deletion; D008928:Mitochondria / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000254:growth & development* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D013997:Time Factors; D015533:Transcriptional Activation; D000099156:Superoxide Dismutase 2
D042967:Electron Transport Complex I; D009245:NADH Dehydrogenase; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C493237:Ndi1 protein, S cerevisiae