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

Table 3 Drugs affecting mitophagy in gastric cancer, colorectal cancer, and inflammatory bowel diseases

Diseases	Drugs	Effects/mechanisms	Significance	Ref.
Gastric cancer	TNFα	Activates Parkin-dependent mitophagy, and excessive mitophagy blocks mitochondrial apoptosis	Relates to the resistance of gastric cancer cells to TNFα	[65]
	Metformin	Activates AMPK signaling pathway and up-regulates the expression of mitophagy-related proteins PINK1, Parkin, and LC3B	Promotes the resistance of gastric cancer cells to cisplatin	[66]
CRC	Mito-CP, mito-metformin	Induces the release of ULK1, which promotes mitophagy	Tumor-suppressing effect: It inhibits tumor proliferation	[78]
	Aloe gel glucomannan	Activates PINK1/Parkin pathway to promote mitophagy; it activates the transcription factor EB to induce mitochondrial damage and ROS generation	Tumor-suppressing effect: It Inhibits tumor proliferation	[79]
	δ-valbetaine	Activates mitophagy through the PINK1/Parkin pathway	Tumor-suppressing effect: Inducing apoptosis of CRC cells	[80]
	Oxymatrine	Induces mitophagy and reduces NLRP3 inflammasome activation in CRC cells	Tumor-suppressing effect: Inhibit the growth and migration of CRC cells	[81]
	Small molecule andrographolide	Inactivates the NLRP3 inflammasome induced by mitophagy in macrophages	Alleviates colitis progression and reduces the risk of colitis-related cancers	[82]
IBD	Sodium butyrate	Activates Pink1/Parkin expression to promote mitophagy; it inhibits phosphorylation of NF-κB and activation of the NLRP3 inflammasome	Has an inhibitory effect on ulcerative colitis	[92]
	NSAIDs	Induces mitochondrial stress which leads to impaired mitophagy	Proinflammatory effects	[89]
	Bergapten	Promotes mitophagy and maintains mitochondrial homeostasis to inhibit NLRP3 inflammasome activation and pyroptosis	Anti-inflammatory activity	[93]
	Ginsenoside Rd	Activates AMPK/ULK1/p62 signaling pathway to trigger mitophagy, thereby inhibiting NLRP3 inflammasome	Anti-inflammatory activity	[94]

CRC: Colorectal cancer; IBD: Inflammatory bowel disease; LC3B: Microtubule-associated proteins light chain 3B; ULK1: UNC-51-like Kinase 1; ROS: Reactive oxygen species; NLRP3: NOD-like receptor thermal protein domain associated protein 3; NSAIDs: Non-steroidal anti-inflammatory drugs.