Mitochondria play a central role in apoptosis (programmed cell death). In particular, the release of proteins, such as cytochrome c and Smac/DIABLO from the mitochondrial intermembrane space into the cytosol is an important trigger for caspase activation, which in turn leads to the events characteristic of apoptosis. Here we propose studies exploring aspects of this apoptotic pathway involving mitochondria. First, we address the interaction of cytochrome c with the Apaf- 1 protein, a step required for caspase-9 activation. Second, we investigate the changes in mitochondrial function resulting from outer membrane permeabilization; under circumstances where caspases are inhibited, these mitochondrial effects may be responsible for the death of the cell. Finally, we explore the nature of the outer mitochondrial membrane permeabilization event, particularly with regard to its regulation by pro- and anti-apoptotic Bcl-2 family proteins such as Bid, Bax and Bcl-xL.
Kushnareva, Y; Seong, Y; Andreyev, A Y et al. (2016) Mitochondrial dysfunction in an Opa1(Q285STOP) mouse model of dominant optic atrophy results from Opa1 haploinsufficiency. Cell Death Dis 7:e2309 |
Kushnareva, Yulia; Andreyev, Alexander Y; Kuwana, Tomomi et al. (2012) Bax activation initiates the assembly of a multimeric catalyst that facilitates Bax pore formation in mitochondrial outer membranes. PLoS Biol 10:e1001394 |
Kushnareva, Yulia; Newmeyer, Donald D (2010) Bioenergetics and cell death. Ann N Y Acad Sci 1201:50-7 |
Lartigue, Lydia; Kushnareva, Yulia; Seong, Youngmo et al. (2009) Caspase-independent mitochondrial cell death results from loss of respiration, not cytotoxic protein release. Mol Biol Cell 20:4871-84 |
Yamaguchi, Ryuji; Lartigue, Lydia; Perkins, Guy et al. (2008) Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell 31:557-69 |