MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells

Article Article scientifique Article MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells eng 2016 author Vanderperre Benoît 818111 author Cermakova Kristina 745156 author Escoffier Breancon Jessica 815071 author Kaba Mayis 820998 author Bender Tom 782667 author Nef Serge 0000-0001-5462-0676 29062 author Martinou Jean-Claude 27293 16448-16461 10.1074/jbc.M116.733840 27317664 0021-9258 Selective transport of pyruvate across the inner mitochondrial membrane by the mitochondrial pyruvate carrier (MPC) is a fundamental step that couples cytosolic and mitochondrial metabolism. The recent molecular identification of the MPC complex has revealed two interacting subunits, MPC1 and MPC2. Although in yeast, an additional subunit, MPC3, can functionally replace MPC2, no alternative MPC subunits have been described in higher eukaryotes. Here, we report for the first time the existence of a novel MPC subunit termed MPC1-like (MPC1L), which is present uniquely in placental mammals. MPC1L shares high sequence, structural, and topological homology with MPC1. In addition, we provide several lines of evidence to show that MPC1L is functionally equivalent to MPC1: 1) when co-expressed with MPC2, it rescues pyruvate import in a MPC-deleted yeast strain; 2) in mammalian cells, it can associate with MPC2 to form a functional carrier as assessed by bioluminescence resonance energy transfer; 3) in MPC1 depleted mouse embryonic fibroblasts, MPC1L rescues the loss of pyruvate-driven respiration and stabilizes MPC2 expression; and 4) MPC1- and MPC1L-mediated pyruvate imports show similar efficiency. However, we show that MPC1L has a highly specific expression pattern and is localized almost exclusively in testis and more specifically in postmeiotic spermatids and sperm cells. This is in marked contrast to MPC1/MPC2, which are ubiquitously expressed throughout the organism. To date, the biological importance of this alternative MPC complex during spermatogenesis in placental mammals remains unknown. Nevertheless, these findings open up new avenues for investigating the structure-function relationship within the MPC complex. Dewey 570 Dewey 576.5 46 Département de biologie cellulaire 165 135 Département de médecine génétique et développement 21D false 448 Mécanismes moléculaires et génétiques du développement sexuel 778 The Journal of biological chemistry 291 32 02602236-79aa-4b28-9e97-dbf49592d498 Article (Published version) Public J. Biol. Chem.-2016-Vanderperre-16448-61.pdf 3907968 application/pdf Restricted 2017-06-26 openAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells	The Journal of biological chemistry	2016	626	371
1. Exploring synthetic lethality of mitochondrial pyruvate carrier knockout cells. 2. MPC1-like: a novel mitochondrial pyruvate carrier subunit		2016	162	12

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Cermakova, Kristina