Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways

Abstract

The assembly of mitochondrial oxidative phosphorylation (OXPHOS) complexes is an intricate process, which—given their dual-genetic control—requires tight co-regulation of two evolutionarily distinct gene expression machineries. Moreover, fine-tuning protein synthesis to the nascent assembly of OXPHOS complexes requires regulatory mechanisms such as translational plasticity and translational activators that can coordinate mitochondrial translation with the import of nuclear-encoded mitochondrial proteins. The intricacy of OXPHOS complex biogenesis is further evidenced by the requirement of many tightly orchestrated steps and ancillary factors. Early-stage ancillary chaperones have essential roles in coordinating OXPHOS assembly, whilst late-stage assembly factors—also known as the LYRM (leucine–tyrosine–arginine motif) proteins—together with the mitochondrial acyl carrier protein (ACP)—regulate the incorporation and activation of late-incorporating OXPHOS subunits and/or co-factors. In this review, we describe recent discoveries providing insights into the mechanisms required for optimal OXPHOS biogenesis, including the coordination of mitochondrial gene expression with the availability of nuclear-encoded factors entering via mitochondrial protein import systems.

MitoQ Is Able to Modulate Apoptosis and Inflammation

“…This evidence suggests that the ATP synthase is correlated with the fusion of the mitochondrial inner membrane regulated by OPA-1 [35]. The fundamental role of this protein in mitochondria stability and in the energy production process is attested by its deficiency in the most common age-related neurodegenerative diseases such as Alzheimer's diseases and Parkinson's disease [34,35,39,40] Moreover, literature data demonstrate that OXPHOS activity was correlated to NLRP3 inflammasome activation in several diseases [41][42][43][44] so much that NLRP3 may be considered as a novel biomarker and therapeutic target for these pathologies [45].…”

“…Moreover, literature data demonstrate that OXPHOS activity was correlated to NLRP3 inflammasome activation in several diseases [ 41 , 42 , 43 , 44 ] so much that NLRP3 may be considered as a novel biomarker and therapeutic target for these pathologies [ 45 ].…”

Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer’s Disease

“…This process is couple to movement of protons from the mitochondrial matrix to the intermembrane space. The proton gradient generated by complexes I, III, and IV is then use to power the rotary turbine-like ATP synthase of complex V, which drives phosphorylation of ADP to ATP [ 69 ]. The energy stored in ATP is then used to meet the immediate energy requirements of cells as well as for biosynthesis, including the synthesis of neurotransmitters, and complex phosphorylation-mediated signaling networks.…”

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

“…It is 16,569-basepair long and includes the heavy chain of the outer ring (high molecular weight) and the light chain of the inner ring (low molecular weight). mtDNA encodes 37 genes, among them, 13 protein-coding regions have been identified to play a role in maintaining normal cellular OXPHOS ( Tang et al, 2020 ). High levels of mitochondrial mutation represent an important factor that leads to dysfunction of oxidative phosphorylation and energy metabolism and endothelial injury ( Ueda et al, 2015 ).…”