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Review
.2009 Feb 23;184(4):469-72.
doi: 10.1083/jcb.200901127.

Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand

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Review

Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand

Vishal M Gohil et al. J Cell Biol..

Abstract

Mitochondrial membrane biogenesis requires the import and synthesis of proteins as well as phospholipids. How the mitochondrion regulates phospholipid levels and maintains a tight protein-to-phospholipid ratio is not well understood. Two recent papers (Kutik, S., M. Rissler, X.L. Guan, B. Guiard, G. Shui, N. Gebert, P.N. Heacock, P. Rehling, W. Dowhan, M.R. Wenk, et al. 2008. J. Cell Biol. 183:1213-1221; Osman, C., M. Haag, C. Potting, J. Rodenfels, P.V. Dip, F.T. Wieland, B. Brügger, B. Westermann, and T. Langer. 2009. J. Cell Biol. 184:583-596) identify novel regulators of mitochondrial phospholipid biosynthesis. The biochemical approach of Kutik et al. (2008) uncovered an unexpected role of the mitochondrial translocator assembly and maintenance protein, Tam41, in the biosynthesis of cardiolipin (CL), the signature phospholipid of mitochondria. The genetic analyses of Osman et al. (2009) led to the discovery of a new class of mitochondrial proteins that coordinately regulate CL and phosphatidylethanolamine, another key mitochondrial phospholipid. These elegant studies highlight overlapping functions and interdependent roles of mitochondrial phospholipid biosynthesis and protein import and assembly.

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Figures

Figure 1.
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.
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References

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