Caspase-independent mitochondrial cell death results from loss of respiration, not cytotoxic protein release.

ABSTRACT: In apoptosis, mitochondrial outer membrane permeabilization (MOMP) triggers caspase-dependent death. However, cells undergo clonogenic death even if caspases are blocked. One proposed mechanism involved the release of cytotoxic proteins (e.g., AIF and endoG) from mitochondria. To initiate MOMP directly without side effects, we created a tamoxifen-switchable BimS fusion protein. Surprisingly, even after MOMP, caspase-inhibited cells replicated DNA and divided for approximately 48 h before undergoing proliferation arrest. AIF and endoG remained in mitochondria. However, cells gradually lost mitochondrial membrane potential and ATP content, and DNA synthesis slowed to a halt by 72 h. These defects resulted from a partial loss of respiratory function, occurring 4-8 h after MOMP, that was not m

SUBMITTER: Lartigue L 

PROVIDER: S-EPMC2785731 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature