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

Mariana Grigoruţă,Alejandro Martínez-Martínez,Ruben K Dagda,Ángel G Díaz-Sánchez

doi:10.1038/s41598-020-66745-9

Mariana Grigoruţă, Alejandro Martínez-Martínez + Show 2 more

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https://doi.org/10.1038/s41598-020-66745-9

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Abstract

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.

Highlights

Psychological distress induces oxidative stress and alters mitochondrial metabolism in the nervous and immune systems
Our study suggests that PTEN-induced kinase 1 (PINK1) is indispensable for maintaining proper mitochondrial metabolism in peripheral blood mononuclear cells (PBMCs) and profiling the bioenergetics in PBMCs may be used as a proxy to inform on: 1) the progression of Parkinson’s disease (PD) pathology and, 2) oxidative stress induced by psychological distress and by PINK1 deficiency
We have previously observed that psychological distress can induce profound alterations in the level of mitochondria, antioxidant response systems and neurotrophic factors which coincided with bioenergetic alterations, presumably due to the high level of oxidative stress induced by psychological distress[3,6,7,8]

Summary

Introduction

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. 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. 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. A balance between mitochondrial biogenesis and mitophagy is crucial in maintaining a proper cell energy metabolism as it maintains a minimum level of functional and high-quality mitochondria required for neuronal survival[13]. Like PINK1-deficient neurons, PINK1-deficient myocytes have high glycolysis rates and show impaired mitochondrial respiration[34]

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