Psychological distress and lack of PINK1 promote bioenergetics alterations in peripheral blood mononuclear cells

• Published in: Scientific reports 2020-06, Vol.10 (1), p.9820-9820, Article 9820
• Main Authors: Grigoruţă, Mariana, Dagda, Ruben K., Díaz-Sánchez, Ángel G., Martínez-Martínez, Alejandro
• Format: Article
• Language: English
• Subjects: 631/250; 631/378; 631/477; 631/80; Animals; Antioxidants; Antioxidants - metabolism; Basal ganglia; Bioenergetics; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cell Respiration; Central nervous system diseases; Energy Metabolism; Female; Gene Expression Regulation; Glycolysis; Humanities and Social Sciences; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; Metabolism; Mitochondria; Mitochondria - metabolism; Movement disorders; multidisciplinary; Neurodegenerative diseases; Oxidative phosphorylation; Oxidative stress; Parkinson's disease; Peripheral blood mononuclear cells; Phosphorylation; Protein Kinases - deficiency; Protein-serine/threonine kinase; Psychological Distress; PTEN protein; PTEN-induced putative kinase; Rats; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-66745-9

Psychological distress induces oxidative stress and alters mitochondrial metabolism in the nervous and immune systems. Psychological distress promotes alterations in brain metabolism and neurochemistry in wild-type (WT) rats in a similar manner as in Parkinsonian rats lacking endogenous PTEN-induced kinase 1 (PINK1), a serine/threonine kinase mutated in a recessive forms of Parkinson’s disease. PINK1 has been extensively studied in the brain, but its physiological role in peripheral tissues and the extent to which it intersects with the neuroimmune axis is not clear. We surmised that PINK1 modulates the bioenergetics of peripheral blood mononuclear cells (PBMCs) under basal conditions or in situations that promote oxidative stress as psychological distress. By using an XF metabolic bioanalyzer, PINK1-KO-PBMCs showed significantly increased oxidative phosphorylation and basal glycolysis compared to WT cells and correlated with motor dysfunction. In addition, psychological distress enhanced the glycolytic capacity in PINK1-KO-PBMCs but not in WT-PBMCs. The level of antioxidant markers and brain-derived neurotrophic factor were altered in PINK1-KO-PBMCs and by psychological distress. In summary, our data suggest that PINK1 is critical for modulating the bioenergetics and antioxidant responses in PBMCs whereas lack of PINK1 upregulates compensatory glycolysis in response to oxidative stress induced by psychological distress.