TY - JOUR
T1 - Polymorphisms of the murine mitochondrial ND4, CYTB and COX3 genes impact hematopoiesis during aging
AU - Kretzschmar, Christin
AU - Roolf, Catrin
AU - Timmer, Katrin
AU - Sekora, Anett
AU - Knübel, Gudrun
AU - Escobar, Hugo Murua
AU - Fuellen, Georg
AU - Ibrahim, Saleh M.
AU - Tiedge, Markus
AU - Baltrusch, Simone
AU - Jaster, Robert
AU - Köhling, Rüdiger
AU - Junghanss, Christian
PY - 2016/9/10
Y1 - 2016/9/10
N2 - During aging, mitochondrial DNA (mtDNA) can accumulate mutations leading to increasing levels of reactive oxygen species (ROS). Increased ROS were described to activate formerly quiescent hematopoietic stem cells (HSC). Mutations in mtDNA were shown to enhance the risk for myelodysplastic syndrome and leukemia. However, the complex relationship between mtDNA variations, ROS and aging of the hematopoietic system is not fully understood. Herein, three mouse strains with mtDNA polymorphisms in genes of respiratory chain complexes I (ND4), III (CYTB) and IV (COX3) were compared to a reference strain during aging. Analysis focused on ROS and ATP levels, bone marrow composition and blood counts. Additionally, hematopoietic restoration capacity following cytotoxic stress was tested. Mice with polymorphisms in ND4 and CYTB gene had significantly decreasing ROS levels in bone marrow cells during aging, without effecting ATP levels. In addition, the frequency of stem and progenitor cells increased during aging but the amount of lymphocytes in the peripheral blood decreased during aging. In summary, the presence of mtDNA polymorphisms affecting the respiratory chain complexes I, III and IV was associated with altered ROS levels as well as changes in BM and peripheral blood composition during aging.
AB - During aging, mitochondrial DNA (mtDNA) can accumulate mutations leading to increasing levels of reactive oxygen species (ROS). Increased ROS were described to activate formerly quiescent hematopoietic stem cells (HSC). Mutations in mtDNA were shown to enhance the risk for myelodysplastic syndrome and leukemia. However, the complex relationship between mtDNA variations, ROS and aging of the hematopoietic system is not fully understood. Herein, three mouse strains with mtDNA polymorphisms in genes of respiratory chain complexes I (ND4), III (CYTB) and IV (COX3) were compared to a reference strain during aging. Analysis focused on ROS and ATP levels, bone marrow composition and blood counts. Additionally, hematopoietic restoration capacity following cytotoxic stress was tested. Mice with polymorphisms in ND4 and CYTB gene had significantly decreasing ROS levels in bone marrow cells during aging, without effecting ATP levels. In addition, the frequency of stem and progenitor cells increased during aging but the amount of lymphocytes in the peripheral blood decreased during aging. In summary, the presence of mtDNA polymorphisms affecting the respiratory chain complexes I, III and IV was associated with altered ROS levels as well as changes in BM and peripheral blood composition during aging.
UR - http://www.scopus.com/inward/record.url?scp=84996878809&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.11952
DO - 10.18632/oncotarget.11952
M3 - Journal articles
C2 - 27626489
AN - SCOPUS:84996878809
SN - 1949-2553
VL - 7
SP - 74460
EP - 74472
JO - Oncotarget
JF - Oncotarget
IS - 46
ER -