Mitochondria-Judges and Executioners of Cell Death Sentences
#MMPMID26942674
Bhola PD
; Letai A
Mol Cell
2016[Mar]; 61
(5
): 695-704
PMID26942674
show ga
Apoptosis is a form of programmed cell death that is critical for basic human
development and physiology. One of the more important surprises in cell biology
in the last two decades is the extent to which mitochondria represent a physical
point of convergence for many apoptosis-inducing signals in mammalian cells.
Mitochondria not only adjudicate the decision of whether or not to commit to cell
death, but also release toxic proteins culminating in widespread proteolysis,
nucleolysis, and cell engulfment. Interactions among BCL-2 family proteins at the
mitochondrial outer membrane control the release of these toxic proteins and, by
extension, control cellular commitment to apoptosis. This pathway is particularly
relevant to cancer treatment, as most cancer chemotherapies trigger
mitochondrial-mediated apoptosis. In this Review, we discuss recent advances in
the BCL-2 family interactions, their control by upstream factors, and how the
mitochondria itself alters these interactions. We also highlight recent clinical
insights into mitochondrial-mediated apoptosis and novel cancer therapies that
exploit this pathway.
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