Mitophagy

Byaibio

Mitophagy is the selective autophagic clearance of damaged mitochondria, a core mitochondrial quality-control pathway that helps maintain cellular homeostasis and cell fate. It is implicated across neurodegeneration, cardiomyopathy, diabetes-related injury, fibrosis, osteoporosis, and infection, and impaired mitophagy can disrupt redox and iron homeostasis, creating a self-amplifying link to ferroptosis. In Alzheimer’s disease, impaired mitophagy is described as a pivotal driver of neurodegeneration, while in cardiomyopathy it is important for disease development and progression. Recent studies also highlight mechanistic regulation by Miro1 ubiquitination, TFAM-induced mitophagy, and Parkin translocation to mitochondria as a hallmark during infection. Therapeutically, mitophagy is being modulated by small molecules, herbal medicines, electroacupuncture, and nanomaterials, including sitagliptin, vildagliptin, kinetin, kakkalide, and palladium-loaded siraitia grosvenorii carbon dots. Overall, the literature positions mitophagy as both a disease biomarker and an intervention point for restoring mitochondrial function and limiting tissue injury.

Neurodegeneration

  • A 2026 Journal of Alzheimer’s Disease review (PMID:41823685) describes impaired mitophagy as a pivotal driver of Alzheimer’s disease neurodegeneration and links it to a self-amplifying ferroptosis loop.
  • Haikun Shenxi Capsule was reported to alleviate Alzheimer’s disease by targeting mitophagy to clear “turbidity toxin” (PMID:41687939).
  • TFAM was reported to induce mitophagy in neurons, and Zhi-Zi-Hou-Po decoction ameliorated depressive-like behaviors via TFAM-induced mitophagy to reduce neuroinflammation (PMID:41702466).
  • Sitagliptin and vildagliptin enhanced mitophagy in neuronal cell lines in a Parkinson’s disease-related study (PMID:41853215).
  • Electroacupuncture at GV20-GB7 regulated mitophagy to protect against neurological deficits after intracerebral hemorrhage, according to the paper title (PMID:41930483).

Cardiovascular and metabolic disease

  • Mitophagy was described as important in the development and progression of cardiomyopathy in a 2026 review (PMID:41944523).
  • In Friedreich’s ataxia hearts, mitochondrial iron overload was associated with lysosomal dysfunction-mediated mitophagy impairment (PMID:41628678).
  • A heart-focused review noted mitophagy as part of mitochondrial homeostasis regulation in cardiac energy metabolism (PMID:41680976).
  • In diabetic nephropathy, ADAMTS13 was reported to ameliorate disease via Nrf2/GPX4/eNOS signaling, while impaired mitophagy was described as part of diabetic kidney mitochondrial dysfunction (PMID:41912450, PMID:41633353).

Tissue repair, inflammation, and fibrosis

  • Kinetin activated mitophagy and mitigated coal-silica mixed dust-induced pulmonary fibrosis by modulating macrophage mitochondrial function in mice (PMID:41894156).
  • Kakkalide promoted spinal cord injury repair via mitophagy and microglial M2 polarization (PMID:41720005).
  • A hydrogen-enriched hyaluronic acid dressing promoted mitophagy to improve diabetic foot ulcer healing (PMID:41906653).
  • A mitochondria-targeted co-assembled nanosystem promoted chronic wound healing by enhancing mitochondrial quality control, including mitophagy-related mechanisms (PMID:41512500).
  • Palladium-loaded siraitia grosvenorii carbon dots amplified mitophagy under near-infrared irradiation to support acute lung injury immunotherapy (PMID:41810016).

Bone and aging-related disease

  • Albiflorin suppressed osteoclast mitophagy via the Rap1a/ERK pathway and alleviated osteoporosis (PMID:41671879).
  • In senescent periosteal mesenchymal stromal/stem cells, mitophagy became severe downstream of mitochondrial dysfunction, linking it to aging-associated poor skeletal repair (PMID:41946679).
  • A study on mitochondrial dysfunction in cerebral amyloidosis highlighted progressive mitochondrial dysfunction as an upstream event in disease progression, with mitophagy discussed in that context (PMID:41637762).

Infection and mechanistic biology

  • During EV-D68 infection, mitophagy hallmarks were induced even though mitochondrial degradation was blocked, indicating uncoupling of initiation and completion (PMID:42018625).
  • Parkin translocation to mitochondria was observed as a hallmark of mitophagy during infection, supporting its role in pathogen response (PMID:41831692).
  • Dihuang Yinzi ameliorated post-stroke depression through Miro1 ubiquitination-dependent mitophagy, providing a specific mechanistic example of pathway control (PMID:41850637).
  • Nanomaterials were described as ideal tools for modulating mitophagy and influencing cell fate, underscoring the platform’s therapeutic versatility (PMID:41831692).