Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation.
BACKGROUND
Neutrophils depend mainly on glycolysis for their energy provision. Their mitochondria maintain a membrane potential (Deltapsi(m)), which is usually generated by the respiratory chain complexes. We investigated the source of Deltapsi(m) in neutrophils, as compared to peripheral blood mononuclear leukocytes and HL-60 cells, and whether neutrophils can still utilise this Deltapsi(m) for the generation of ATP.


RESULTS
Individual activity of the oxidative phosphorylation complexes was significantly reduced in neutrophils, except for complex II and V, but Deltapsi(m) was still decreased by inhibition of complex III, confirming the role of the respiratory chain in maintaining Deltapsi(m). Complex V did not maintain Deltapsi(m) by consumption of ATP, as has previously been suggested for eosinophils. We show that complex III in neutrophil mitochondria can receive electrons from glycolysis via the glycerol-3-phosphate shuttle. Furthermore, respiratory supercomplexes, which contribute to efficient coupling of the respiratory chain to ATP synthesis, were lacking in neutrophil mitochondria. When HL-60 cells were differentiated to neutrophil-like cells, they lost mitochondrial supercomplex organisation while gaining increased aerobic glycolysis, just like neutrophils.


CONCLUSIONS
We show that neutrophils can maintain Deltapsi(m) via the glycerol-3-phosphate shuttle, whereby their mitochondria play an important role in the regulation of aerobic glycolysis, rather than producing energy themselves. This peculiar mitochondrial phenotype is acquired during differentiation from myeloid precursors.
van Raam
Bram J
BJ
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
Sluiter
Wim
W
de Wit
Elly
E
Roos
Dirk
D
Verhoeven
Arthur J
AJ
Kuijpers
Taco W
TW
D000255:Adenosine Triphosphate / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010641:Phenotype; D010710:Phosphates / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D010710:Phosphates; D014475:Uncoupling Agents; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D014450:Electron Transport Complex III