SBK2-Driven NDUFV1 Phosphorylation and Translocation Limits Cardiac Hypertrophy - PubMed
5 hours ago
- #cardiac hypertrophy
- #NDUFV1 phosphorylation
- #SBK2
- Cross-species transcriptomic screening and UK Biobank analyses identified cardiac-enriched kinase SBK2 as linked to heart failure risk.
- SBK2 expression is reduced in hypertrophic hearts, and its overexpression attenuates hypertrophy and fibrosis while improving systolic function.
- SBK2 phosphorylates NDUFV1 at serine 251, enhancing interaction with HSPA1A and facilitating mitochondrial import via TOM70.
- Increased mitochondrial NDUFV1 promotes complex I activity, supercomplex assembly, oxidative phosphorylation, and mitochondrial fusion.
- Pharmacological inhibition of complex I or NDUFV1 silencing abolishes SBK2-mediated protection against hypertrophy.
- The SBK2-NDUFV1 axis links cytosolic kinase signaling to mitochondrial proteostasis, limiting pathological cardiac hypertrophy.