Trends in Cell Biology

Trends in Cell Biology

Volume 28, Issue 1, January 2018, Pages 67-76
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Review
Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics

https://doi.org/10.1016/j.tcb.2017.08.011Get rights and content

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Mitochondrial fusion and division play important roles in mitochondrial size, number, distribution, function, and turnover.

Cardiolipin (CL) promotes both mitochondrial division and inner membrane fusion.

Phosphatidic acid (PA) inhibits mitochondrial division and stimulates mitochondrial outer membrane fusion.

Recent studies have identified phospholipases and lipid phosphatases, such as mitochondria-localized phospholipase D (MitoPLD), PA-preferring phospholipase A1 (PA-PLA1), and lipin 1b, that control the levels of CL and PA in mitochondria.

Lipid-modifying enzymes could provide mechanisms that coordinate mitochondrial dynamics.

Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases. Moreover, lipid-modifying enzymes such as phospholipases and lipid phosphatases may organize local lipid composition to spatially and temporarily coordinate a balance between fusion and division to establish mitochondrial morphology.

Section snippets

Mitochondrial Dynamics: Fusion and Division

Mitochondria play crucial roles in diverse cellular and physiological processes such as energy production, metabolism, intracellular signaling, cell death, development, and immune response. In these functions mitochondria serve as a bioenergetic power plant and a dynamic signaling hub. It has become increasingly clear that these mitochondrial functions are important for human health and that defects in these processes lead to pathological consequences such as metabolic diseases, cancer,

Critical Phospholipids for Mitochondrial Dynamics: PA and CL

Mitochondria comprise two distinct but physically connected membranes: the outer and inner membranes. The primary lipid components in the mitochondrial membrane are phospholipids, while sphingolipids and cholesterols are relatively uncommon compared with other membranes, such as the plasma membrane 36, 37. Two major phospholipids in the mitochondrial membranes are phosphatidylcholine (PC) and phosphatidylethanolamine (PE), each of which contributes 30–40% of the total phospholipids in

Concluding Remarks

During the past 20 years, many protein components that mediate mitochondrial dynamics have been identified. In addition, the post-translational modifications of these proteins in response to a variety of signals and stressors have been characterized. However, there are many crucial open questions regarding the role of lipids and their regulation in the membrane-remodeling processes in mitochondria (see Outstanding Questions). Because protein–lipid interactions are fundamental to membrane fusion

Acknowledgments

The authors thank members of the Okamoto, Iijima, and Sesaki laboratories for helpful discussions. This work was supported by grants to M.I. (NIH GM084015, WW Smith Charitable Trust, and Allegheny Health Network-Sidney Kimmel Comprehensive Cancer Center), to H.S. (Allegheny Health Network-Sidney Kimmel Comprehensive Cancer Center and JHU-UMD Diabetes Research Center), and to K.O. and H.S. (Osaka University International Joint Research Promotion Program).

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