Mitochondrial membrane dynamics, cristae remodelling and apoptosis

Abstract

Mitochondria form a highly dynamic reticular network in living cells, and undergo continuous fusion/fission events and changes in ultrastructural architecture. Although significant progress has been made in elucidating the molecular events underlying these processes, their relevance to normal cell function remains largely unexplored. Emerging evidence, however, suggests an important role for mitochondrial dynamics in cellular apoptosis. The mitochondria is at the core of the intrinsic apoptosis pathway, and provides a reservoir for protein factors that induce caspase activation and chromosome fragmentation. Additionally, mitochondria modulate Ca2+ homeostasis and are a source of various metabolites, including reactive oxygen species, that have the potential to function as second messengers in response to apoptotic stimuli. One of the mitochondrial factors required for activation of caspases in most intrinsic apoptotic pathways, cytochrome c, is largely sequestered within the intracristae compartment, and must migrate into the boundary intermembrane space in order to allow passage across the outer membrane to the cytosol. Recent evidence argues that inner mitochondrial membrane dynamics regulate this process. Here, we review the contribution of mitochondrial dynamics to the intrinsic apoptosis pathway, with emphasis on the inner membrane.

Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins

“…Mitochondrial fragmentation, as a result of altered morphological dynamics, has been implicated in mitochondrial injury during apoptosis (11)(12)(13)(14). Our results now further suggest that the mitochondrial fragmentation may involve Bak.…”

“…Recent studies have revealed a striking morphological change of mitochondria during apoptosis (11)(12)(13)(14). Upon apoptotic stimulation, mitochondria collapse from a filamentous network into punctate fragments.…”

The role of mitochondria in apoptosis

“…The OMM surrounds an IMM which encloses a protein-rich matrix containing the mitochondrial DNA. The large surface area of the IMM in relation to that of the OMM necessitates organization of the IMM into numerous invaginations, or cristae (63,64). Mammalian cells maintain the overall shape of their mitochondria by balancing the opposing processes of mitochondrial fusion and fission (1,7).…”

Autophagy, Mitochondria and Cell Death in Lysosomal Storage Diseases

“…37,38 It should be noted, however, that mitochondrial morphology is dynamic and mitochondrial fragmentation precedes apoptosis in several systems. 39,40 As LSD cells are more sensitive to apoptosis, 18 the possibility remains that mitochondrial fragmentation in our system reflects pre-apoptotic changes.…”