Table 2.

Targeting Mitophagy in Disease

Tissue	Disease	Characteristics	Approach	Reference Nos.
Brain	Parkinson’s disease	Defects in mitophagy, reduced mitochondrial biogenesis and mitochondrial dysfunction. Loss of dopaminergic neurons.	Increase or restore mitophagy	21, 82, 134, 159, 225, 300
	Alzheimer’s disease	Accumulation of dysfunctional mitochondria, formation of Aβ plaques and neurofibrillary tangles. Loss of neurons and synapses.	Increase autophagy/mitophagy	128, 162, 166, 177, 210, 333, 334
	Huntington disease	Misfolding of Htt leading to formation of cytotoxic aggregates. Defects in autophagy cargo recognition and inhibition of micromitophagy. Accumulation of damaged mitochondria and increased cell death.	Increase autophagy and mitophagy	111, 178, 242, 255
	Amyotrophic lateral sclerosis	Mutations in genes linked to regulation of autophagy/mitophagy. Decreased mitophagy and loss of motor neurons.	Increase autophagy or restore mitophagy	132, 194, 247, 321
Heart	Myocardial infarction	Mitophagy is activated in response to ischemic/energetic stress. Impaired mitophagy leads to accumulation of damaged mitochondria, loss of myocytes, and heart failure development.	Increase mitophagy	112, 147, 267, 309
	Pressure overload	Autophagy and mitophagy are increased during the acute phase of pressure overload but decreased in the chronic phase. Decreased mitophagy correlates with accumulation of dysfunctional mitochondria and cardiac dysfunction.	Increase mitophagy	18, 98, 264
	Doxorubicin-induced cardiotoxicity	Controversial studies have reported both recued and increased mitophagy after exposure to the drug.	Unclear	105, 109
Various tissues	Cancer	Mitophagy functions as a tumor suppressor mechanism in certain cancers. Impaired mitophagy correlates with enhanced cancer development.	Unclear	39, 50, 71, 78, 163, 259, 305, 340
Lungs	Acute lung injury	Increased mitophagy protects lung cells against hyperoxia, S. aureus infection and sepsis.	Increase autophagy/mitophagy	175, 286, 343
	Chronic obstructive pulmonary disease	Controversial: insufficient mitophagy leads to senescence of lung epithelial cells, while enhanced mitophagy leads to activation of necroptosis in lung epithelial cells. Both conditions contribute to COPD.	Unclear	115, 193
	Idiopathic pulmonary fibrosis	Alteration in mitophagy is cell dependent.	Unclear	6, 137, 154, 224
		Increased mitophagy in alveolar macrophages leads to apoptosis resistance and increased inflammation. Reduced mitophagy in fibroblasts enhances the fibrotic response.
Liver	Alcoholic liver disease and acetaminophen overdose	Activation of autophagy and mitophagy protect against mitochondrial damage and liver injury.	Increase autophagy/mitophagy	204, 208, 318
Immune system	Inflammation	Impaired autophagy/mitophagy leads to the reduced elimination of pathogens. Impaired mitophagy also leads to excess NLRP3 inflammasome activation and chronic inflammation.	Increase autophagy/mitophagy	4, 131, 176, 190, 198, 344, 345

COPD, chronic obstructive pulmonary disease.