Working Paper Review Version 1 This version is not peer-reviewed

Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain by Omics Technologies

Version 1 : Received: 16 June 2021 / Approved: 17 June 2021 / Online: 17 June 2021 (15:12:01 CEST)

How to cite: Zanfardino, P.; Doccini, S.; Santorelli, F.M.; Petruzzella, V. Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain by Omics Technologies. Preprints 2021, 2021060466 Zanfardino, P.; Doccini, S.; Santorelli, F.M.; Petruzzella, V. Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain by Omics Technologies. Preprints 2021, 2021060466

Abstract

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria although the land-scape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding de-tails to the mitochondrial proteome and defining novel metabolic cellular interrelations, espe-cially 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 as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ 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 determination of the OxPhos complexes is one of the reasons for the complexity of the geno-type-phenotype correlation when facing human diseases associated with mitochondria defects; clinically, are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the fu-ture directions of the multi-omics study of human brain disorders.

Subject Areas

mitochondria; mitochondrial DNA; nervous tissue, OxPhos complexes; bioenergetics; genomics; proteomics; mitochondrial diseases

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