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. 2009 Feb 23;184(4):469–472. doi: 10.1083/jcb.200901127

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© 2009 Gohil and Greenberg

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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Figure 1. — Identification of novel regulators of mitochondrial nonbilayer-forming phospholipids. (A) Interdependence of CL biosynthesis and function. Four enzymatic steps catalyze CL biosynthesis in the inner mitochondrial membrane (IMM). The genes encoding three steps have been identified. Import machinery for proteins with N-terminal cleavable sequences (Tim23) or internal signals (Tim22) is also localized in the IMM. The newly identified Tam41 regulates Tim23- and Tim22-dependent protein import as well as CL biosynthesis, possibly by activating Cds1. CL, in turn, regulates protein import by maintaining the IMM potential by a mechanism not currently understood. CL stabilizes supercomplex assembly of complex III and IV, and stimulates complex IV activity. The pH gradient generated by respiratory chain activity increases CL synthesis by activating Crd1 synthase activity. (B) Genetic interactome of prohibitins regulates PE and/or CL levels. Genes identified in a synthetic genetic screen as genetic interactors of prohibitins (Phb1/2) consist of three classes that regulate (1) CL levels, (2) PE levels, or (3) both CL and PE. CDP-DG, cytidine diphosphodiacylglycerol; CL, cardiolipin; PA, phosphatidic acid; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PGP, phosphatidylglycerolphosphate.