Missing lipid shrinks heart and lowers exercise capacity

Phospholipase A and acyltransferase 1, or PLAAT1, is an enzyme that catalyzes lipid-modifying reactions. Under laboratory conditions, PLAAT1 produces a lipid known as cardiolipin. Cardiolipin is essential for the inner mitochondrial membrane because it stabilizes respiratory complexes and ATP synthase to support energy metabolism; thereby, influencing diverse biological processes, including growth, cardiorespiratory function and exercise capacity. However, the impact of PLAAT1 loss in living organisms remains unknown. To address this, Ashkan Hashemi and colleagues from the University of Waterloo, in collaboration with a team of researchers in Scotland, generated mice lacking the PLAAT1 gene and compared them to mice expressing PLAAT1. They published their results in the Journal of Lipid Research.

The authors observed that PLAAT1-deficient mice had similar body weights to their normal counterparts, although males ate less. Their hearts were noticeably smaller — 14.2% smaller in males and 10.6% smaller in females — and cardiolipin content in the heart dropped by approximately one-third, primarily due to a loss of the linoleate-rich form of the lipid. Additionally, these hearts contained reduced amounts of succinate dehydrogenase complex flavoprotein subunit A, a mitochondrial protein vital for energy metabolism. PLAAT1 deficiency also diminished oxygen consumption, carbon dioxide production and total energy expenditure. While general activity levels remained similar, exercise capacity was impaired in both male and female mice.

Together, these findings highlight PLAAT1 as a critical regulator of cardiolipin composition, mitochondrial function and systemic energy metabolism, with direct consequences for cardiovascular performance and potential links to mitochondrial disease.