Table 1.

Changes of mitophagy observed with age or in PD and AD, which are related to oxidative stress.

Mitophagy Pathway or Protein	Age Related Changes	Changes in PD or AD
Pink/Parkin	Depletion of Pink1 and Parkin leads to hallmarks of senescence in ISCs (Intestinal stem cells) of D. melanogaster, including high ROS levels [94]; Overexpression of Pink1 or Parkin extends lifespan of D. melanogaster [95]; Parkin overexpression attenuates molecular and biochemical markers of aging, extending lifespan in D. melanogaster [196] mRNA levels of BNIP3, PINK1, Parkin and NIX, and the protein levels of BNIP3, PINK1 and Parkin decrease in the mouse auditory cortex with aging [197]; Parkin levels are diminished in atrophied muscles of elderly men [98]; Parkin overexpression attenuates the effects of advanced aging on myocardial function in transgenic mice [198] Parkin overexpression attenuates aging-dependent loss of muscle strength and mass in transgenic mice [97].	Upregulation of the PINK1/parkin pathway were showed in AD patients’ brain [119,120]; Depletion of Parkin during AD progression were found in AD patients’ brain [121]; Low levels of the Parkin protein were identified in skin fibroblasts and brain biopsies from AD patients [122]; Increased levels of Parkin were revealed in a transgenic mouse model [123]; Homozygous or compound heterozygous mutations and the consequent loss of function of Parkin and PINK1 genes are the main cause of recessive early-onset PD [159,119]; Mutations in PINK1 gene are also a rare source of sporadic early-onset PD [160].
Cardiolipin	Cardiolipin levels in mitochondria decrease with aging [134]; Changes to cardiolipin content and oxidative damage have been related to aging in hearts of rats; no direct evidence of cardiolipin-mitophagy impairment has been provided [35,133].	Changes in the cardiolipin profile were described in mouse model of AD [126]; Correlation between oxidative damage of CL by ROS and pathogenesis of PD, likely because of the impairment of mitophagy caused by damaged CL. No direct evidence is provided [199].
DJ-1	DJ-1 mutants in D. melanogaster exhibit lifespan shortening and sensitivity to oxidative stress; Repressed during aging in rat thymus tissues [200].	Immunostaining revealed high levels of DJ-1 protein in hippocampal pyramidal neurons and astrocytes of AD brains [201]; Mutations in DJ-1 gene are cause of autosomal recessive PD [161]; Fibroblasts and lymphoblasts from PD patients with mutated DJ-1 showed fragmented mitochondria [151,153]. Mutations in Dj-1 impaired protection against oxidative stress, a key regulator of the neurodegenerative process in PD and AD [202,203,204,205,206,207,208,209,210]
BNIP3	mRNA levels of BNIP3, PINK1, Parkin and NIX, and the protein levels of BNIP3, PINK1 and Parkin in the mouse auditory cortex decrease with aging [197].	No data available
MFN1	Age-related increase of MFN1 and OPA1 in cultured fibroblasts.	Increased expression in neurons from patients with AD.
MFN1/MFN2	MFN2 expression is higher in rat and human chondrocytes during aging and OA (osteoarthritis) [101] MFN2 decreases during aging in mouse skeletal muscle [99].	Reduced levels of MFN1, MFN2 and OPA1 were found in aged tau mice [132]; Changes of MFN1 and MFN2 were identified both in the PrP-hAPP/hPS1 AD mouse model brains and in an SH-SY5Y cell model of early-onset AD [211]. Decreased levels of mitochondrial fusion proteins, MFN1, MFN2 and OPA1 were found in 12-month-old tau mice relative to age-matched WT mice [132].