Cyclase-associated protein 1 facilitates actin-dependent mitochondrial fission in podocytes associated with diabetic nephropathy.

Aberrant mitochondrial dynamics in podocytes are closely associated with the progression of diabetic nephropathy (DN); however, the underlying mechanisms remain incompletely understood. Recent research has demonstrated that cyclase-associated protein 1 (CAP1), an actin-binding protein, mediates mitochondrial fission. Therefore, we aimed to explore the regulatory role and mechanisms of CAP1 in high glucose (HG)-induced mitochondrial dysfunction in podocytes. CAP1 knockout reduced the severity of glomerular injuries and curtailed mitochondrial fission in podocytes in streptozotocin (STZ)-induced DN models. Subsequently, we observed that HG levels induced the mitochondrial translocation of CAP1 in podocytes, and CAP1 inhibition mitigated excessive mitochondrial fission. Mechanistically, our findings demonstrate that CAP1 facilitates HG-induced mitochondrial fission in podocytes by modulating actin reorganization. Furthermore, we present evidence that CAP1 interacts with Cofilin1, and this interaction plays a role in enhancing HG-induced mitochondrial fission in podocytes. This study elucidates the critical role of CAP1 in facilitating HG-induced mitochondrial fission in podocytes by regulating actin dynamics. These findings offer novel insights for the prevention and treatment of DN.