Review Volume 14, Issue 6 pp 2902—2919

Mitophagy and mitochondrial dynamics in type 2 diabetes mellitus treatment

Zhao Shan1, , Wei Hong Fa1, , Chen Run Tian1, , Chen Shi Yuan1, , Ning Jie1, ,

  • 1 Department of Endocrinology, Shenzhen Longhua District Central Hospital, Guangdong Medical University Afliated Longhua Central Hospital, Shenzhen 518110, Guangdong, China

Received: August 13, 2021       Accepted: December 3, 2021       Published: March 24, 2022
How to Cite

Copyright: © 2022 Shan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The prevalence of type 2 diabetes is associated with inflammatory bowels diseases, nonalcoholic steatohepatitis and even a spectrum of cancer such as colon cancer and liver cancer, resulting in a substantial healthcare burden on our society. Autophagy is a key regulator in metabolic homeostasis such as lipid metabolism, energy management and the balance of cellular mineral substances. Mitophagy is selective autophagy for clearing the damaged mitochondria and dysfunctional mitochondria. A myriad of evidence has demonstrated a major role of mitophagy in the regulation of type 2 diabetes and metabolic homeostasis. It is well established that defective mitophagy has been linked to the development of insulin resistance. Moreover, insulin resistance is further progressed to various diseases such as nephropathy, retinopathy and cardiovascular diseases. Concordantly, restoration of mitophagy will be a reliable and therapeutic target for type 2 diabetes. Recently, various phytochemicals have been proved to prevent dysfunctions of β-cells by mitophagy inductions during diabetes developments. In agreement with the above phenomenon, mitophagy inducers should be warranted as potential and novel therapeutic agents for treating diabetes. This review focuses on the role of mitophagy in type 2 diabetes relevant diseases and the pharmacological basis and therapeutic potential of autophagy regulators in type 2 diabetes.


AMPK: AMP-activated protein kinase; ATG: Autophagy related genes; Drp1: Dynamin-related protein 1; FIS 1: mitochondrial fission 1 protein; FUNDC1: FUN14 domain-containing 1; GSC: Ginseng-Sanqi-Chuanxiong; HDAC: histone deacetylase; KEAP1: Kelch-like ECH-associated protein 1; LAMP1: lysosomal associated membrane protein-1; LC3: microtubule-associated protein 1A1B-light chain3; MITF: microphthalmia-associated transcription factor; mTORC1: mTOR complex 1; Nrf 2: nuclear factor E2-related factor 2; p38 MAPK: p38 mitogen-activated protein kinase; p62/SQSTM1: ubiquitin and sequestosome-1; PARKIN: ubiquitin ligase; PGC-1α: peroxisome proliferator-activated receptor γ coactivator-1α; PI3K: phosphor-inositide 3 kinase; PI3P: phosphatidylinositol-3-phosphate; PINK1: PTEN-induced putative kinase 1; SIRT1/3: sirtuin 1/3; STZ: Streptozotocin; TFE3: transcription factor E3; TFEB: transcription factor EB; TGF-β1: transforming growth factor beta 1; UCP1: uncoupling protein 1; VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3.