Akila T Moore et al. (2005) International Worm Meeting "The Conserved C. elegans Mitochondrial Protein Prohibitin Plays a Critical Role in Proper Transition of Meiotic Cells"

Akila T Moore, Andy Golden, Clive Shiff

[International Worm Meeting, 2005]

Prohibitin is a conserved mitochondrial protein that is involved in numerous activities in the cell including cell cycle(1), apoptosis(2), and chaperone activity in the mitochondria(3). Previous studies have also shown that prohibitin is critical for embryogenesis and germline activity in C. elegans(4). We have demonstrated that embryonic lethality in the depletion of phb-2 by RNAi is due to chromosome segregation defects that stem from problems during meiosis. Surprisingly, depletion of phb-2 in mutants that bypass the spindle checkpoint (mdf-2 and mdf-3) at the metaphase to anaphase transition significantly suppresses embryonic lethality in phb-2 depletion. This suggests that the inability to activate specific cell cycle checkpoints in the depletion of phb-2 significantly rescues embryonic lethality placing prohibitin at a specific juncture in the cell cycle process. 1. Ikonen, E., et al. (1995) FEBS Letters 385: 273-277; 2. Joshi, B., et al. (2003) Biochem and Biophys Research Comm 312; 459-466; 3. Nijtmans, L., Grivell, L., et al. (2000) EMBO 19: 2444-2451; 4. Sanz, M., Nijtmans, L. et al. (2003) J Bio Chem 278:32091-32099 124341

Sanz MA et al. (2003) J Biol Chem "The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans."

Tsang WY, Willems EM, van der Spek H, Lemire BD, Sanz MA, Grivell LA, Nijtmans LGJ

[J Biol Chem, 2003]

Prohibitins in eukaryotes consist of two subunits (PHB1 and PHB2) that together form a high molecular weight complex in the mitochondrial inner membrane. The evolutionary conservation and the ubiquitous expression in mammalian tissues of the prohibitin complex suggest an important function among eukaryotes. The PHB complex has been shown to play a role in the stabilization of newly synthesized subunits of mitochondrial respiratory enzymes in the yeast Saccharomyces cerevisiae. We have used Caenorhabditis elegans as model system to study the role of the PHB complex during development of a multicellular organism. We demonstrate that prohibitins in C. elegans form a high molecular weight complex in the mitochondrial inner membrane similar to that of yeast and humans. By using RNA-mediated gene inactivation, we show that PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad. We further demonstrate that a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells. This paper reports a strong loss of function phenotype for prohibitin gene inactivation in a multicellular organism and shows for the first time that prohibitins serve an essential role in mitochondrial function during organismal development.

Artal-Sanz M et al. (2003) J Biol Chem "The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans."

Nijtmans LGJ, Artal-Sanz M, van der Spek H, Lemire BD, Grivell LA, Tsang WY, Willems EM

[J Biol Chem, 2003]

Dr. Artal-Sanz's name was incorrectly listed. The corrected version is shown above.