PRKCI-NIPSNAP1 Axis Regulates Mitophagy in Intestinal Ischemia–Reperfusion Injury

Intestinal ischemia–reperfusion (I/R) injury is a life-threatening condition associated with intestinal barrier disruption and multiple organ dysfunction. Although mitophagy plays an important role in maintaining cellular homeostasis, its regulatory mechanisms in intestinal I/R injury remain incompletely understood. Using data-independent acquisition (DIA) proteomics, we identified protein kinase C iota (PRKCI) as a differentially expressed protein associated with intestinal I/R injury. Immunoprecipitation–mass spectrometry (IP-MS) and protein–protein interaction analysis identified NipSnap homolog 1 (NIPSNAP1) as a potential PRKCI-interacting protein, and their association was further validated by co-immunoprecipitation (Co-IP). PRKCI silencing or NIPSNAP1 overexpression enhanced mitophagy-related responses, reduced reactive oxygen species accumulation, preserved mitochondrial membrane potential, and attenuated apoptosis. Functional rescue experiments further supported the involvement of NIPSNAP1 in the effects associated with PRKCI silencing. Collectively, these findings support a role for the PRKCI/NIPSNAP1 axis in modulating mitophagy during intestinal I/R injury and highlight this axis as a potential therapeutic target.