A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers.
The assessment of metabolic function in cells isolated from human blood for treatment and diagnosis of disease is a new and important area of translational research. It is now becoming clear that a broad range of pathologies which present clinically with symptoms predominantly in one organ, such as the brain or kidney, also modulate mitochondrial energetics in platelets and leukocytes allowing these cells to serve as "the canary in the coal mine" for bioenergetic dysfunction. This opens up the possibility that circulating platelets and leukocytes can sense metabolic stress in patients and serve as biomarkers of mitochondrial dysfunction in human pathologies such as diabetes, neurodegeneration and cardiovascular disease. In this overview we will describe how the utilization of glycolysis and oxidative phosphorylation differs in platelets and leukocytes and discuss how they can be used in patient populations. Since it is clear that the metabolic programs between leukocytes and platelets are fundamentally distinct the measurement of mitochondrial function in distinct cell populations is necessary for translational research.
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Philip A
PA
Kramer
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Saranya
S
Ravi
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Balu
B
Chacko
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Michelle S
MS
Johnson
Department of Pathology, UAB Mitochondrial Medicine Laboratory, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Victor M
VM
Darley-Usmar
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism; D005544:Forecasting; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism* / Q000648:ultrastructure; D024821:Metabolic Syndrome / Q000097:blood; D008928:Mitochondria / Q000502:physiology*; D009369:Neoplasms / Q000097:blood; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress
D015415:Biomarkers; D000255:Adenosine Triphosphate
Biomarker; ECAR, extracellular acidification rate; Leukocytes; Metabolic shift; OCR, oxygen consumption rate; Oxidative stress; Platelets; ROS/RNS, reactive oxygen species/reactive nitrogen species; Reserve capacity; XF, extracellular flux analyzer