Mitochondrial dynamics modulation

Mitochondrial dynamics modulation refers to the therapeutic regulation of the continuous cycles of fission and fusion that maintain mitochondrial morphology, quality, and function [PubMed: 22464331]. This process is governed by key GTPases, including Dynamin-1-like protein (DRP1) for fission, and Mitofusins (MFN1/2) and Optic Atrophy 1 (OPA1) for fusion [Nature Reviews Molecular Cell Biology, 2012]. Dysregulation of these dynamics is a hallmark of various pathologies, including neurodegenerative diseases like Parkinson's and Alzheimer's, where excessive fission leads to mitochondrial fragmentation and cell death [Science, 2008]. In cardiovascular diseases, impaired dynamics contribute to ischemia-reperfusion injury and heart failure by disrupting energy production and calcium handling [Circulation Research, 2013]. Pharmacological intervention aims to restore the balance between fission and fusion to improve mitochondrial health and cellular survival [Cell Metabolism, 2013]. Small molecules like Mdivi-1 and P110 target DRP1 to inhibit excessive fission, while others like Leflunomide promote fusion by upregulating MFN2 [Frontiers in Pharmacology, 2020]. While promising, targeting these fundamental processes poses significant challenges regarding tissue specificity and potential off-target effects on global cellular metabolism [Pharmacological Reviews, 2019].

Other names

Mitochondrial fission and fusionMitochondrial remodelingMitochondrial morphology regulation

Modulation involves the pharmacological inhibition of fission-promoting proteins like DRP1 or the activation of fusion-promoting proteins such as MFN1, MFN2, and OPA1 to restore mitochondrial network integrity [Frontiers in Pharmacology, 2020].