P INK1/PARKIN mitophagy: a potential regulator of mitochondrial homeostasis in functional dyspepsia
TL;DR
A narrative review elaborates the molecular regulatory mechanisms of the PINK1/PARKIN pathway and proposes a tentative pathological cascade: impaired PINK1/PARKIN signaling – defective mitophagy – gastrointestinal dysmotility, visceral hypersensitivity and chronic low-grade inflammation – FD onset and progression.
Abstract
Functional dyspepsia (FD) is a highly prevalent functional gastrointestinal disorder with limited long-term treatment efficacy and high recurrence rates, while its upstream pathogenic mechanisms remain incompletely defined. Mitochondrial dysfunction and defective mitophagy represent key pathological events underlying FD pathogenesis. Beyond the PINK1/PARKIN-dependent ubiquitinated mitophagy cascade, the non-ubiquitin BNIP3/NIX mitophagy axis also mediates gastrointestinal mitochondrial quality control under hypoxic and inflammatory stimuli. As the canonical signaling pathway governing mitophagy and mitochondrial homeostasis, the PINK1/PARKIN axis potentially participates in regulating gastrointestinal energy metabolism, restraining oxidative stress, modulating visceral sensation, and maintaining mucosal barrier integrity. This narrative review elaborates the molecular regulatory mechanisms of the PINK1/PARKIN pathway and proposes a tentative pathological cascade: impaired PINK1/PARKIN signaling – defective mitophagy – gastrointestinal dysmotility, visceral hypersensitivity and chronic low-grade inflammation – FD onset and progression. We further summarize prominent unresolved research gaps in this field. Further investigations targeting this pathway may offer novel theoretical foundations and promising intervention targets for precision diagnosis and management of FD.