The dual role of TRPC channel-mediated dysregulation of calcium signaling in regulating mitophagy in early brain injury after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) induces early brain injury (EBI) through mechanisms involving mitochondrial dysfunction and dysregulated calcium signaling. Transient receptor potential canonical (TRPC) channels are critical mediators of calcium homeostasis and have emerged as key players in SAH pathophysiology. This review explores the interconnected roles of TRPC channel-mediated calcium dyshomeostasis and mitophagy in EBI. We summarize how mitochondrial damage post-SAH triggers mitophagy via ubiquitin-dependent and -independent pathways, a process with dual effects on neuronal survival. We then detail the dual-phase roles of TRPC subtypes: early neuroprotection via TRPC1/4 and later exacerbation of injury via TRPC3/6/7, linking their activation to vascular dysfunction and inflammation. Crucially, we propose and discuss the mechanistic links through which TRPC-mediated calcium signals may directly regulate mitophagic flux, thereby influencing EBI outcomes. Targeting this TRPC-mitophagy axis with subtype- and temporal-specific strategies holds therapeutic promise for SAH.