Mitochondrial Respiratory Chain Dysfunction-A Hallmark Pathology of Idiopathic Parkinson's Disease?

Irene H Flønes; Charalampos Tzoulis

doi:10.3389/fcell.2022.874596

Mitochondrial Respiratory Chain Dysfunction-A Hallmark Pathology of Idiopathic Parkinson's Disease?

Front Cell Dev Biol. 2022 Apr 1:10:874596. doi: 10.3389/fcell.2022.874596. eCollection 2022.

Authors

Irene H Flønes^{1

2

3}, Charalampos Tzoulis^{1

2

3}

Affiliations

¹ Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
² K.G Jebsen Center for Translational Research in Parkinson's Disease, University of Bergen, Bergen, Norway.
³ Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Abstract

Parkinson's disease (PD) is the most common age-dependent neurodegenerative synucleinopathy. Loss of dopaminergic neurons of the substantia nigra pars compacta, together with region- and cell-specific aggregations of $α$ -synuclein are considered main pathological hallmarks of PD, but its etiopathogenesis remains largely unknown. Mitochondrial dysfunction, in particular quantitative and/or functional deficiencies of the mitochondrial respiratory chain (MRC), has been associated with the disease. However, after decades of research in this field, the pervasiveness and anatomical extent of MRC dysfunction in PD remain largely unknown. Moreover, it is not known whether the observed MRC defects are pathogenic, compensatory responses, or secondary epiphenomena. In this perspective, we give an overview of current evidence for MRC dysfunction in PD, highlight pertinent knowledge gaps, and propose potential strategies for future research.

Keywords: Parkinson's disease; mitochondria; mitochondrial complex I; neurodegeneration; oxidative phosphorylation.