Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain

• Published in: International journal of molecular sciences 2021-08, Vol.22 (15), p.8325
• Main Authors: Zanfardino, Paola, Doccini, Stefano, Santorelli, Filippo M, Petruzzella, Vittoria
• Format: Article
• Language: English
• Subjects: Animals; Bioenergetics; Bioinformatics; Brain Diseases - metabolism; Brain Diseases - pathology; Energy Metabolism; Genes; Genomes; Genomics; Genotypes; Homeostasis; Humans; Localization; Mass spectrometry; Metabolism; Metabolites; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; mitochondrial DNA; Morphology; Mutation; Nervous system; nervous tissue; Oxidative Phosphorylation; OxPhos complexes; Phenotypes; Phosphorylation; Proteins; Proteomes; Proteomics; Review; Scientific imaging; Signs and symptoms
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22158325

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of - technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ' ', ' ' and ' ' have entered the field of 'mitochondrial medicine'. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism, mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic origin of the OxPhos complexes is one of the reasons for the complexity of the genotype-phenotype correlation when facing human diseases associated with mitochondrial defects. Such complexity clinically manifests with extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the future directions of the multi-omics study of human brain disorders.