Mitochondria in precision medicine; linking bioenergetics and metabolomics in platelets
Balu K. Chacko,
Matthew R. Smith,
Michelle S. Johnson,
Gloria Benavides,
Matilda L. Culp,
Jyotsna Pilli,
Sruti Shiva,
Karan Uppal,
Young-Mi Go,
Dean P. Jones,
Victor M. Darley-Usmar
Affiliations
Balu K. Chacko
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK
Matthew R. Smith
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory School of Medicine, Atlanta, GA, USA
Michelle S. Johnson
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK
Gloria Benavides
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK
Matilda L. Culp
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK
Jyotsna Pilli
Department of Pharmacology & Chemical Biology, Vascular Medicine Institute, Center for Metabolism & Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Sruti Shiva
Department of Pharmacology & Chemical Biology, Vascular Medicine Institute, Center for Metabolism & Mitochondrial Medicine, University of Pittsburgh, Pittsburgh, PA, USA
Karan Uppal
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory School of Medicine, Atlanta, GA, USA
Young-Mi Go
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory School of Medicine, Atlanta, GA, USA
Dean P. Jones
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, Emory School of Medicine, Atlanta, GA, USA
Victor M. Darley-Usmar
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK; Corresponding author.
Mitochondria possess reserve bioenergetic capacity, supporting protection and resilience in the face of disease. Approaches are limited to understand factors that impact mitochondrial functional reserve in humans. We applied the mitochondrial stress test (MST) to platelets from healthy subjects and found correlations between energetic parameters and mitochondrial function. These parameters were not correlated with mitochondrial complex I-IV activities, however, suggesting that other factors affect mitochondrial bioenergetics and metabolism. Platelets from African American patients with sickle cell disease also differed from controls, further showing that other factors impact mitochondrial bioenergetics and metabolism. To test for correlations of platelet metabolites with energetic parameters, we performed an integrated analysis of metabolomics and MST parameters. Subsets of metabolites, including fatty acids and xenobiotics correlated with mitochondrial parameters. The results establish platelets as a platform to integrate bioenergetics and metabolism for analysis of mitochondrial function in precision medicine.
