Vital function of PRELI and essential requirement of its LEA motif.
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McKeller MR, Herrera-Rodriguez S, Ma W, Ortiz-Quintero B, Rangel R, Cande C, Sims-Mourtada JC, Melnikova V, Kashi C, Phan LM, Chen Z, Huang P, Dunner K Jr, Kroemer G, Singh KK, Martinez-Valdez H
Vital function of PRELI and essential requirement of its LEA motif.
Cell Death Dis. 2010;1:e21. doi: 10.1038/cddis.2009.19.
- PubMed ID
- 21364629 [ View in PubMed]
- Abstract
Proteins containing the late embryogenesis abundant (LEA) motif comprise a conserved family, postulated to act as cell protectors. However, their function and mechanisms of action remain unclear. Here we show that PRELI, a mammalian LEA-containing homolog of yeast Ups1p, can associate with dynamin-like GTPase Optic Atrophy-1 (OPA1) and contribute to the maintenance of mitochondrial morphology. Accordingly, PRELI can uphold mitochondrial membrane potential (DeltaPsi(m)) and enhance respiratory chain (RC) function, shown by its capacity to induce complex-I/NADH dehydrogenase and ATP synthase expression, increase oxygen consumption and reduce reactive oxygen species (ROS) production. PRELI can also inhibit cell death induced by STS, TNF-alpha or UV irradiation. Moreover, in vitro and in vivo dominant-negative overexpression of mutant PRELI/LEA(-) (lacking the LEA motif) and transient in vitro PRELI-specific knockdown can render lymphocytes vulnerable to apoptosis, cause mouse embryo lethality and revert the resistance of lymphoma cells to induced death. Collectively, these data support the long-presumed notion of LEA protein-dependent mechanisms of cytoprotection and suggest that PRELI interacts with OPA1 to maintain mitochondria structures intact, sustain balanced ion(-)/proton(+) gradients, promote oxidative phosphorylation reactions, regulate pro- and antiapoptotic protein traffic and enable cell responses to induced death. These findings may help to understand how bioenergetics is mechanistically connected with cell survival cues.