C3- and C5-deficient murine cells exhibit severe mitochondrial defects, indicating a pivotal, novel role of innate immunity in regulating hematopoiesis at the electron transfer chain level
- 1Center for Preclinical Studies and Technology, Laboratory of Regenerative Medicine at Medical University of Warsaw, Warsaw, Poland
- 2Laboratory of Electron Microscopy of the Center for Translational Research, Nencki Institute of Experimental Biology, Warsaw, Poland
- 3Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY USA
Abstract
We recently reported that the functional intracellular complement network, known as the complosome, is expressed in hematopoietic stem/progenitor cells (HSPCs). In our recent work, murine lineage-negative (Lin−) bone marrow (BM) mononuclear cells (BMMNC) from C3-KO and C5–/– mice showed defects in oxygen consumption rate (OCR) and elevated lactate production, along with increased lactate dehydrogenase (LDH) release, indicating dependence on anaerobic glycolysis. Simultaneously, mitochondria from C3 and C5 complosome mutant Lin-BMMNC accumulated fewer MitoTracker probes, suggesting mitochondrial defects. To better understand these changes, we focused on the expression of (i) key enzymes involved in aerobic and anaerobic glycolysis, (ii) genes involved in mitochondrial quality control (MCQ), (iii) the electron transfer chain (ETC) activity of all five ETC complexes, and (iv) TEM analysis of mitochondrial morphology in purified murine Lin- BMMNC. Our data confirm that the complosome is important for maintaining proper mitochondrial development and function, as C3 and C5 mutants exhibit severe defects in complex I and III activity and display an increase in the number of immature and damaged mitochondria. To our knowledge, this is the first study conducted on cells enriched in HSPCs to directly demonstrate functional defects in the ETC in C3- and C5 complosome-deficient cells. These data are crucial for all studies that use C3- and C5-deficient mice to investigate immune responses, tissue and organ regeneration, aging, or behavioral processes, and provide solid evidence for a pivotal novel role for innate immunity in regulating hematopoiesis.
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BibTeX
@article{kazek2026c5deficient,
title = {{C3- and C5-deficient murine cells exhibit severe mitochondrial defects, indicating a pivotal, novel role of innate immunity in regulating hematopoiesis at the electron transfer chain level}},
author = {Michalina Kazek and Damian Wojdalski and Adrian Konopko and Patrycja Kieszek and Agnieszka Lukomska and Kannathasan Thetchinamoorthy and Hanna Nieznańska and Magdalena Świadek and Emilia Waraksa-Zasada and Janina Ratajczak and Magdalena Kucia and Mariusz. Z. Ratajczak},
journal = {Leukemia},
year = {2026},
month = sep,
doi = {10.1038/s41375-026-03134-7},
url = {https://doi.org/10.1038/s41375-026-03134-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - C3- and C5-deficient murine cells exhibit severe mitochondrial defects, indicating a pivotal, novel role of innate immunity in regulating hematopoiesis at the electron transfer chain level
AU - Michalina Kazek
AU - Damian Wojdalski
AU - Adrian Konopko
AU - Patrycja Kieszek
AU - Agnieszka Lukomska
AU - Kannathasan Thetchinamoorthy
AU - Hanna Nieznańska
AU - Magdalena Świadek
AU - Emilia Waraksa-Zasada
AU - Janina Ratajczak
AU - Magdalena Kucia
AU - Mariusz. Z. Ratajczak
PY - 2026
DA - 2026/09/22
JO - Leukemia
DO - 10.1038/s41375-026-03134-7
UR - https://doi.org/10.1038/s41375-026-03134-7
AB - We recently reported that the functional intracellular complement network, known as the complosome, is expressed in hematopoietic stem/progenitor cells (HSPCs). In our recent work, murine lineage-negative (Lin−) bone marrow (BM) mononuclear cells (BMMNC) from C3-KO and C5–/– mice showed defects in oxygen consumption rate (OCR) and elevated lactate production, along with increased lactate dehydrogenase (LDH) release, indicating dependence on anaerobic glycolysis. Simultaneously, mitochondria from C3 and C5 complosome mutant Lin-BMMNC accumulated fewer MitoTracker probes, suggesting mitochondrial defects. To better understand these changes, we focused on the expression of (i) key enzymes involved in aerobic and anaerobic glycolysis, (ii) genes involved in mitochondrial quality control (MCQ), (iii) the electron transfer chain (ETC) activity of all five ETC complexes, and (iv) TEM analysis of mitochondrial morphology in purified murine Lin- BMMNC. Our data confirm that the complosome is important for maintaining proper mitochondrial development and function, as C3 and C5 mutants exhibit severe defects in complex I and III activity and display an increase in the number of immature and damaged mitochondria. To our knowledge, this is the first study conducted on cells enriched in HSPCs to directly demonstrate functional defects in the ETC in C3- and C5 complosome-deficient cells. These data are crucial for all studies that use C3- and C5-deficient mice to investigate immune responses, tissue and organ regeneration, aging, or behavioral processes, and provide solid evidence for a pivotal novel role for innate immunity in regulating hematopoiesis.
SN - 0887-6924
SN - 1476-5551
ER -