The role of mitochondrial dynamics in disease

Abstract

Mitochondria are multifaceted and dynamic organelles regulating various important cellular processes from signal transduction to determining cell fate. As dynamic properties of mitochondria, fusion and fission accompanied with mitophagy, undergo constant changes in number and morphology to sustain mitochondrial homeostasis in response to cell context changes. Thus, the dysregulation of mitochondrial dynamics and mitophagy is unsurprisingly related with various diseases, but the unclear underlying mechanism hinders their clinical application. In this review, we summarize the recent developments in the molecular mechanism of mitochondrial dynamics and mitophagy, particularly the different roles of key components in mitochondrial dynamics in different context. We also summarize the roles of mitochondrial dynamics and target treatment in diseases related to the cardiovascular system, nervous system, respiratory system, and tumor cell metabolism demanding high‐energy. In these diseases, it is common that excessive mitochondrial fission is dominant and accompanied by impaired fusion and mitophagy. But there have been many conflicting findings about them recently, which are specifically highlighted in this view. We look forward that these findings will help broaden our understanding of the roles of the mitochondrial dynamics in diseases and will be beneficial to the discovery of novel selective therapeutic targets.

Type 2 diabetes microenvironment promotes the development of Parkinson’s disease by activating microglial cell inflammation

“…PD is a common neurodegenerative disease with a complex pathogenesis, with previous studies showing a close association between mitochondrial dysfunction and PD ( Golpich et al, 2017 ; Mounsey and Teismann, 2011 ). Mitochondrial dysfunction in PD has been linked to various factors, including the pathogenic genes PINK/PRKN associated with PD causing mitochondrial dysfunction in neurons ( Xu et al, 2020 ; Wang et al, 2023 ). Environmental factors such as exposure to organic compounds or pesticides have also been found to disrupt mitochondrial bioenergetics and electron transport chain function, leading to various forms of mitochondrial damage ( Jayasundara, 2017 ; Roubicek and Souza-Pinto, 2017 ).…”

Targeting Mitochondrial Dynamics during Lower-Limb Ischemia Reperfusion in Young and Old Mice: Effect of Mitochondrial Fission Inhibitor-1 (mDivi-1)

“…Experimental models demonstrated various effects concerning limb protection when using ischemic or pharmacological pre-and post-conditioning [6,19], but mitochondrial dynamic modulation might be promising since it plays a critical role in controlling mitochondrial morphology and energetic metabolism [20][21][22][23]. Mitochondrial fission modulation with the mitochondrial division inhibitor-1 (mDivi-1), known as an inhibitor of dynaminrelated protein 1 (Drp1) function, demonstrated protective effects in the setting of IR in several organs, including kidneys, brain, and heart [24][25][26][27][28][29][30].…”