Roles of mitochondria in neutrophils

Abstract

Neutrophils are the most abundant leukocyte in human blood. They are critical for fighting infections and are involved in inflammatory diseases. Mitochondria are indispensable for eukaryotic cells, as they control the biochemical processes of respiration and energy production. Mitochondria in neutrophils have been underestimated since glycolysis is a major metabolic pathway for fuel production in neutrophils. However, several studies have shown that mitochondria are greatly involved in multiple neutrophil functions as well as neutrophil-related diseases. In this review, we focus on how mitochondrial components, metabolism, and related /Sungenes regulate neutrophil functions and relevant diseases.

Neutrophil immune profile controls spinal cord regeneration in zebrafish

“…Our neutrophil-specific RNA-seq data reveals that blocking this signaling axis induces upregulation of the mitochondrial oxidative phosphorylation (OXPHOS), proteasome, phagosome, lysosome, and metabolic pathways. Mitochondrial OXPHOS is involved in regulating respiratory burst, development, and migration [68, 69], whereas phagosome and proteasome pathways are intrinsic to neutrophil activity. Therefore, our results suggest that inhibiting Cxcr4 signaling increases neutrophil cellular activity, switching them towards a more “defensive” state and potentially a pro-resolution phenotype.…”

The metabolic basis of inherited neutropenias

“…dinucleotide phosphate (NADPH) and ribulose 5-phosphate, an important precursor for nucleotide biosynthesis. 21,22 When a cell needs more NADPH than nucleotides, the excess of ribulose 5-phosphate is converted to compounds that can enter glycolysis. NADPH is an essential electron donor that serves as a major component for redox balance in neutrophils and plays an essential role in oxidative burst.…”

“…They have important functions in both haematopoietic stem cells, such as quiescence, self-renewal, and lineage differentiation 24 and neutrophils, such as chemotaxis, respiratory burst, neutrophil extra-cellular trap (NET) formation, differentiation and cell death. 21 Defects in TAFAZZIN and HAX1 affect the mitochondria, resulting in neutropenia (discussed below). Interestingly, the number of mitochondria in neutrophils is lower than that of other cells.…”

“…Alternatively, glucose‐6‐phosphate can enter the pentose phosphate pathway (PPP), a parallel metabolic pathway to glycolysis that generates nicotinamide adenine dinucleotide phosphate (NADPH) and ribulose 5‐phosphate, an important precursor for nucleotide biosynthesis 21,22 . When a cell needs more NADPH than nucleotides, the excess of ribulose 5‐phosphate is converted to compounds that can enter glycolysis.…”

“…Mitochondria are essential for energy production via the electron transport chain (ETC) and OXPHOS to generate ATP in cells. They have important functions in both haematopoietic stem cells, such as quiescence, self‐renewal, and lineage differentiation 24 and neutrophils, such as chemotaxis, respiratory burst, neutrophil extra‐cellular trap (NET) formation, differentiation and cell death 21 . Defects in TAFAZZIN and HAX1 affect the mitochondria, resulting in neutropenia (discussed below).…”