Stomatin-Like Protein 2 Binds Cardiolipin and Regulates Mitochondrial Biogenesis and Function

Abstract

Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane protein of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 and binds to the mitochondrial membrane phospholipid cardiolipin. Upregulation of SLP-2 expression increases cardiolipin content and the formation of metabolically active mitochondrial membranes and induces mitochondrial biogenesis. In human T lymphocytes, these events correlate with increased complex I and II activities, increased intracellular ATP stores, and increased resistance to apoptosis through the intrinsic pathway, ultimately enhancing cellular responses. We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. Likely through the prohibitin functional interactome, SLP-2 then regulates mitochondrial biogenesis and function.

ACKNOWLEDGMENTS

We thank Heidi McBride, Jean-Claude Martinou, Fred Possmayer, and the members of the Madrenas laboratory for helpful discussions in the course of this work.

This research was supported by the Canadian Institutes of Health Research. D.A.C. holds a CIHR Doctoral Studentship. G.M.H. holds a Canada Research Chair in Molecular Cardiolipin Metabolism, and J.M. holds a Canada Research Chair in Immunobiology.