Abstract
Several studies suggest that the assembly of mitochondrial respiratory complexes into structures known as supercomplexes (SCs) may increase the efficiency of the electron transport chain, reducing the rate of production of reactive oxygen species. Therefore, the study of the (dis)assembly of SCs may be relevant for the understanding of mitochondrial dysfunction reported in brain aging and major neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Here we briefly reviewed the biogenesis and structural properties of SCs, the impact of mtDNA mutations and mitochondrial dynamics on SCs assembly, the role of lipids on stabilization of SCs and the methodological limitations for the study of SCs. More specifically, we summarized what is known about mitochondrial dysfunction and SCs organization and activity in aging, AD and PD. We focused on the critical variables to take into account when postmortem tissues are used to study the (dis)assembly of SCs. Since few works have been performed to study SCs in AD and PD, the impact of SCs dysfunction on the alteration of brain energetics in these diseases remains poorly understood. The convergence of future progress in the study of SCs structure at high resolution and the refinement of animal models of AD and PD, as well as the use of iPSC-based and somatic cell-derived neurons, will be critical in understanding the biological relevance of the structural remodeling of SCs.
Highlights
Mitochondria are dynamic organelles that reorganize under stress or variations in the availability of nutrients or oxygen
It was postulated that COX7A2L may be a regulatory checkpoint for the biogenesis of CIII2 and complex III (CIII)-containing SCs [19] while Rcf1 and Rcf2 are complex IV (CIV)-binding proteins that may interact with CIII2 [20]
These observations suggest that oxidative phosphorylation (OXPHOS) complex assembly and function may be modulated by oxidative stress and mitochondrial dynamics, probably involving the fission/fusion machinery [91, 92]. These findings support that mitochondrial dysfunction in Parkinson’s disease (PD) may require, among other pathways, the structural remodeling of SCs. It was shown in postmortem samples of the frontal cortex of Alzheimer’s disease (AD) subjects a significant decrease in the levels of complex II (CII), CIII, and CV subunits as compared to controls, while a strong tendency was found for decrements on CIV levels and no differences were detected in complex I (CI) [93]
Summary
Mitochondria are dynamic organelles that reorganize under stress or variations in the availability of nutrients or oxygen. It was proposed that an equilibrated distribution between individual mitochondrial respiratory complexes (MRC) and supercomplexes (SCs) is relevant to achieve the optimal performance of the electron transfer chain. The procedures by which the assembly of SCs can be adapted to the requirements of the cells are still poorly understood. In this mini review we address the organization of SCs in cell cultures and brain tissue from human or animal models of aging, AD and PD to evaluate the possible relevance of the (dis)assembly of SCs in the energetic failures characteristics of these neurodegenerative disorders associated with amyloid deposition
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