From macroautophagy to mitophagy: Unveiling the hidden role of mitophagy in gastrointestinal disorders

Table 2 Pathways regulating mitophagy in gastric cancer, colorectal cancer, and inflammatory bowel diseases

Diseases	Molecules	Effects/mechanisms	Significance	Ref.
Gastric cancer	Yap	Activates the SIRT1/Mfn2/mitophagy axis. Knockdown of Yap impairs the expression of adhesive proteins, reduces F-actin expression, and inhibits lamellipodium formation	Tumor-promoting effects: It contributes to the migration and survival of gastric cancer cells	[63]
	GGT7	Binds with the mitophagy regulator RAB7 to induce mitophagy. GGT7 inhibits ROS production and MAPK cascades	Tumor-suppressing effect: It inhibits the growth, G1-S phase transition and migration of gastric cancer cells	[64]
CRC	piR823	Promotes ubiquitination and proteasome-dependent degradation of PINK1, thereby inhibiting mitophagy	Tumor-promoting effects: It is involved in CRC tumorigenesis	[71]
	MST1	Inhibits mitophagy through the JNK/p53/BNIP3 pathway, leading to oxidative stress and initiating mitochondria-mediated apoptosis	Tumor-suppressing effect: It inhibits tumor proliferation	[73]
	GPR176	Inhibits mitophagy through the cAMP/PKA/BNIP3L axis	Tumor-promoting effects: It promotes the development of CRC	[74]
IBD	NR1D1	Acts as a positive regulator of BNIP3 expression, promoting mitophagy and maintaining the immune homeostasis of IECs	Inhibitory effect on colitis: It reduces the severity and progression of colitis	[88]

CRC: Colorectal cancer; IBD: Inflammatory bowel diseases; Yap: Yes-associatide protein; GGT7: Gamma-glutamyltransferase 7; SIRT1: Sirtuin 1; Mfn2: Mitofusin 2; JNK: c-Jun N-terminal kinase; BNIP3: BCL2-interacting protein 3; BNIP3L: BCL2-interacting protein 3 like; IECs: Intestinal epithelial cells; MST1: Mammalian sterile 20-like kinase 1; GPR176: G protein-coupled receptors 176; PKA: Protein kinase A; NR1D1: Nuclear receptor subfamily 1 group D member 1.