Mitophagy and mitochondrial dynamics in type 2 diabetes mellitus treatment

Abstract

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.

Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease

“…IR occurs due to an imbalance between the supply and demand of nutrients in multiple tissues, including skeletal muscle, liver, and adipose tissue [57]. It is also associated with mitochondrial dysfunction [58]. In addition, mitochondrial dysfunction contributes greatly to age-dependent IR [59] and induces diabetic microvascular (cardiomyopathy, nephropathy, retinopathy, and neuropathy) [60][61][62][63] and macrovascular (myocardial ischemia) [64] complications.…”

Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview

“…Thus, several antioxidants are proposed to eliminate ROS. These include caffeine, curcumin, and various vitamins, as shown in a study by Shan et al [ 223 ]. Mitophagy can be inhibited by pharmacological inhibition of lysosomal acidification conducted in vitro by Yang et al [ 224 ].…”

Miro proteins and their role in mitochondrial transfer in cancer and beyond

“…Dysregulation of mitophagy (and calcium signaling) is linked to many pathologies, starting with neurological diseases such as Parkinson disease (PD), heart failure, metabolic disorders, aging and cancer ( Lahiri and Klionsky, 2017 ; Kay et al, 2018 ; Pickles et al, 2018 ; Cao et al, 2019 ; Kesharwani et al, 2019 ; Berenguer-Escuder et al, 2020 ; Brunelli et al, 2020 ; Eberhardt et al, 2020 ; Imai, 2020 ; Denisenko et al, 2021 ; Nahacka et al, 2021 ; Zhang et al, 2021 ; Babula and Krizanova, 2022 ; Diao and Gustafsson, 2022 ; Lee et al, 2022 ; Shan et al, 2022 ). Miro proteins are important regulators of the process of mitophagy, firstly prior to mitochondrial damage where they serve as calcium sensors, translocating Parkin to mitochondria, and then as Parkin downstream targets where ubiquitination of Miro proteins arrests mitochondrial trafficking needed for the organelle removal ( Nahacka et al, 2021 ).…”