Coenzyme Q homeostasis in aging: Response to non-genetic interventions

Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases

“…Simvastatin promotes the translocation of Parkin and p62/SQSTM1 and activates mitophagy, thus inhibiting the infarct size in cellular and mouse myocardial infarction models [ 99 ]. Coenzyme Q exerts its anti-ischemic function by disturbing mitophagy [ 100 ]. Liraglutide facilitates myocardial restoration to inhibit myocardial infarction by the upregulation of SIRT1 and Parkin, activation of mitophagy, reduction in cellular oxidative stress, optimum redox state, and mitochondrial homeostasis [ 101 ].…”

Coenzyme Q at the Hinge of Health and Metabolic Diseases

“…Most of the redaction reactions of CoQ come from NADH-dependent complex I and FADH 2 -dependent complex II. However, CoQ is also reduced by diverse oxidoreductases, which represents key steps in important metabolic pathways, such as iron sulfur cluster synthesis, nucleotide synthesis, and sulfide metabolism [ 39 , 40 ]. These reactions and their metabolic mechanisms have been recently reviewed by [ 41 ].…”

“…In these redox activities, the redox state of CoQ determines where and how electrons move from the electron carrier and if leaks produce reactive oxygen species (ROS) [ 42 ]. Although free radicals have long been thought to be responsible for aging and age-related diseases, recent reports indicate that they have both positive and negative effects on longevity and health acting as integrators of cellular homeostasis [ 39 , 42 , 43 , 44 ]. The levels of CoQ, its redox state, and its interaction with CoQ-dependent enzymatic activities can be key in the modulation of cellular homeostasis.…”

“…The CoQ-dependent redox reactions in the mitochondria are linked directly or indirectly to oxidative phosphorylation (OXPHOS), in which electrons flow through mitochondrial complexes to generate the proton gradient necessary for ATP synthesis, until they finally reach oxygen to reduce it to water [ 39 ], additionally affecting diverse metabolic pathways [ 41 ].…”

“…MitoNEET, also known as CDGS1 iron sulfur domain 1 (CISD1) protein, is a redox-active and pH-sensing protein that regulates energy metabolism, iron homeostasis, and ROS in mitochondria. MitoNEET interacts with reduced flavin mononucleotide (FMNH2) that reduces mitoNEET sulfoferric [2Fe–2S] clusters, which are oxidized back with CoQ being the most efficient electron acceptor [ 39 , 57 ]. As one of the proteins repaired by MitoNEET is the iron-master regulator IRP-1, which limits iron access to mitochondria to protect against ferroptosis in high ROS production, CoQ can be considered as an important redox-sensing factor in the adaptive response against oxidative injury, and a key component in the prevention of ferroptosis caused by mitochondrial dysfunction [ 39 ].…”