Heart failure & cardiomyopathies
Vacuolar H + -ATPase Preserves Cardiolipin Homeostasis Through the Lysosomal-Mitochondrial Axis to Restrain Cardiac Aging
Authors' conclusion
Augmenting v-ATPase-mediated lysosomal acidification offers novel therapeutic strategies to combat age-related cardiomyopathy by rewiring CL homeostasis.
Study context
- Population
- Aging mouse models and elderly people (cardiac aging)
- Outcome
- Mechanism of age-related cardiomyopathy
Methodological detailsCrls1 knockout mouse model, 2 v-ATPase knockout models, aging mouse models and elderly people
- Crls1 knockout mouse model
- 2 v-ATPase knockout models
- Aging mouse models and elderly people
Main finding
As reported in the abstract
- Declining cardiac NAD levels impair v-ATPase-mediated lysosomal acidification by weakening the aldolase–v-ATPase interaction
- Reduced lysosomal acidification increases lysosomal membrane permeability, allowing cathepsin B to leak into mitochondria
- Cathepsin B disrupts mitochondrial CRLS1, impairing cardiolipin (CL) synthesis and remodelling
- CL deficiency causes mitochondrial oxidative stress and programmed cell death, leading to mitochondrial and cardiac dysfunction
- Genetic or chemical inhibition of v-ATPase and of CRLS1 in mouse models reproduces these age-related defects
- Restoring NAD levels rescues lysosomal acidification and CL metabolism, protecting against age-related cardiomyopathy in rodents and humans
Original publication
Vacuolar H + -ATPase Preserves Cardiolipin Homeostasis Through the Lysosomal-Mitochondrial Axis to Restrain Cardiac Aging. Circulation. Published 17 June 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →