Vital function of PRELI and essential requirement of its LEA motif

Academic Article

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 (ΔAΦm) 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-α 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. © 2010 Macmillan Publishers Limited.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 7505047
  • Author List

  • McKeller MR; Herrera-Rodriguez S; Ma W; Ortiz-Quintero B; Rangel R; Candé C; Sims-Mourtada JC; Melnikova V; Kashi C; Phan LM
  • Volume

  • 1
  • Issue

  • 2