The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans.
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
Marta
M
Swammerdam Institute for Life Sciences, Section for Molecular Biology, University of Amsterdam, Kruislaan 318, Amsterdam 1098 SM, The Netherlands. artal@science.uva.nl
Tsang
William Y
WY
Willems
Esther M
EM
Grivell
Les A
LA
Lemire
Bernard D
BD
van der Spek
Hans
H
Nijtmans
Leo G J
LG
Sanz
Marta Artal
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D005854:Germ Cells / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D000091402:Prohibitins; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C000717328:PHB protein, human; C000717329:PHB1 protein, S cerevisiae; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C000717338:prohibitin 2, C elegans