Mitochondrial intermembrane proteins in cell death

Abstract

Apoptosis is a form of programmed cell death important in the development and tissue homeostasis of multicellular organisms. Mitochondria have, next to their function in respiration, an important role in the apoptotic-signaling pathway. Malfunctioning at any level of the cell is eventually translated in the release of apoptogenic factors from the mitochondrial intermembrane space resulting in the organized demise of the cell. Some of these factors, such as AIF and endonuclease G, appear to be highly conserved during evolution. Other factors, like cytochrome c, have gained their apoptogenic function later during evolution. In this review, we focus on the role of cytochrome c, AIF, endonuclease G, Smac/DIABLO, Omi/HtrA2, Acyl-CoA-binding protein, and polypyrimidine tract-binding protein in the initiation and modulation of cell death in different model organisms. These mitochondrial factors may contribute to both caspase-dependent and caspase-independent processes in apoptotic cell death.

Alterations of intracellular pH homeostasis in apoptosis: origins and roles

“…Are alterations of pH iregulating mechanisms involved? (2) What is the exact role (initiator or activator) of this acidification in the apoptotic cascade and what are its cellular targets?…”

“…What are the mechanisms targeted by the alkalinization responsible for such a decision? (2) What are the mechanims underlying the transient activation of NHE1 upon apoptotic stimuli? With respect to the latter issue, Khaled et al 61 have suggested that the alkaline pH i itself might secondarily inhibit the p38 MAPK pathway.…”

“…Besides these two major types of apoptosis, several cases of caspase-independent apoptosis have been reported, implicating apoptosis-inducing factor (AIF) as a determinant regulator. 1,2 In contrast, little is understood about the accompanying changes in intracellular ionic homeostasis, although there exists a certain amount of work on apoptosis-associated variations in Ca 2 þ i , K þ i and H þ i . As the role of Ca 2 þ i and K þ i in apoptosis has been recently reviewed, 3 the present review will essentially focus on H þ i homeostasis and will discuss recent advances in this field.…”

Expression of antiapoptotic and proapoptotic molecules in diabetic retinas

“…18,21,[23][24][25][26] Bad is a proapoptotic member of the Bcl-2 gene family that promotes apoptosis by binding to and inhibiting functions of antiapoptotic proteins Bcl-2 and Bcl-xL. 10,27 Mitochondria play a key role in the control of apoptotic cell death. Early during the apoptotic process, mitochondria can release several apoptogenic proteins, such as cytochrome c and AIF, into the cytosol.…”

“…Early during the apoptotic process, mitochondria can release several apoptogenic proteins, such as cytochrome c and AIF, into the cytosol. 27,28 The death domain containing adaptors TRADD and FADD act as pivotal proteins in the mechanism of ligandinduced programmed cell death (apoptosis) originating at the Fas (CD 95/APO-1) and tumour necrosis factor type 1 receptors. Recruitment of caspase-8 through TRADD and FADD results in caspase activation and subsequent apoptosis.…”