Mitochondrial Phospholipid Metabolism in Health and Disease

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2023 Sep 1

PMID 37655851

Authors

Alaumy Joshi

Travis H Richard

Vishal M Gohil

Affiliations

Soon will be listed here.

Abstract

Studies of rare human genetic disorders of mitochondrial phospholipid metabolism have highlighted the crucial role that membrane phospholipids play in mitochondrial bioenergetics and human health. The phospholipid composition of mitochondrial membranes is highly conserved from yeast to humans, with each class of phospholipid performing a specific function in the assembly and activity of various mitochondrial membrane proteins, including the oxidative phosphorylation complexes. Recent studies have uncovered novel roles of cardiolipin and phosphatidylethanolamine, two crucial mitochondrial phospholipids, in organismal physiology. Studies on inter-organellar and intramitochondrial phospholipid transport have significantly advanced our understanding of the mechanisms that maintain mitochondrial phospholipid homeostasis. Here, we discuss these recent advances in the function and transport of mitochondrial phospholipids while describing their biochemical and biophysical properties and biosynthetic pathways. Additionally, we highlight the roles of mitochondrial phospholipids in human health by describing the various genetic diseases caused by disruptions in their biosynthesis and discuss advances in therapeutic strategies for Barth syndrome, the best-studied disorder of mitochondrial phospholipid metabolism.

Citing Articles

Functional Specialization of S-Adenosylmethionine Synthases Links Phosphatidylcholine to Mitochondrial Function and Stress Survival.

Munden A, Lui D, Higgins D, Fanelli M, Ngyuen T, Edwards K bioRxiv. 2025; .

PMID: 40027629 PMC: 11870525. DOI: 10.1101/2025.02.20.639242.

Alterations in Lipid Saturation Trigger Remodeling of the Outer Mitochondrial Membrane.

Wong S, Bertram K, Raghuram N, Knight T, Hughes A bioRxiv. 2025; .

PMID: 39896499 PMC: 11785037. DOI: 10.1101/2025.01.20.633997.

Triacylglycerol mobilization underpins mitochondrial stress recovery.

Baker Z, Zhu Y, Guerra R, Smith A, Arra A, Serrano L Nat Cell Biol. 2025; 27(2):298-308.

PMID: 39779944 PMC: 11821527. DOI: 10.1038/s41556-024-01586-6.

Proteolytic regulation of mitochondrial magnesium channel by m-AAA protease and prohibitin complex.

Joshi A, Stanfield R, Spletter A, Gohil V Genetics. 2024; 229(2).

PMID: 39657011 PMC: 11796461. DOI: 10.1093/genetics/iyae203.

Phosphatidylethanolamine.

Primrose M, Claypool S Trends Endocrinol Metab. 2024; 35(10):929-930.

PMID: 39426372 PMC: 11490686. DOI: 10.1016/j.tem.2024.06.011.

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