World J Mens Health.  2022 Jul;40(3):399-411. 10.5534/wjmh.210146.

The Role of Mitochondrial Dynamic Dysfunction in Age-Associated Type 2 Diabetes

• Vezza T
• Díaz-Pozo P
• Canet F
• de Marañón AM
• Abad-Jiménez Z
• García-Gargallo C
• Roldan I
• Solá E
• Bañuls C
• López-Domènech S
• Rocha M
• Víctor VM

• KMID: 2530708
• DOI: http://doi.org/10.5534/wjmh.210146

Abstract

Mitochondrial dynamics, such as fusion and fission, play a critical role in maintaining cellular metabolic homeostasis. The molecular mechanisms underlying these processes include fusion proteins (Mitofusin 1 [MFN1], Mitofusin 2 [MFN2], and optic atrophy 1 [OPA1]) and fission mediators (mitochondrial fission 1 [FIS1] and dynamin-related protein 1 [DRP1]), which interact with each other to ensure mitochondrial quality control. Interestingly, defects in these proteins can lead to the loss of mitochondrial DNA (mtDNA) integrity, impairment of mitochondrial function, a severe alteration of mitochondrial morphology, and eventually cell death. Emerging evidence has revealed a causal relationship between dysregulation of mitochondria dynamics and age-associated type 2 diabetes, a metabolic disease whose rates have reached an alarming epidemic-like level with the majority of cases (59%) recorded in men aged 65 and over. In this sense, fragmentation of mitochondrial networks is often associated with defects in cellular energy production and increased apoptosis, leading, in turn, to excessive reactive oxygen species release, mitochondrial dysfunction, and metabolic alterations, which can ultimately contribute to β-cell dysfunction and insulin resistance. The present review discusses the processes of mitochondrial fusion and fission and their dysfunction in type 2 diabetes, with special attention given to the therapeutic potential of targeting mitochondrial dynamics in this complex metabolic disorder.

Keyword

Aging; Men; Mitochondria; Type 2 diabetes