Splenic compensation alleviates impaired-development of bone marrow terminal erythroid to attenuate anemia in ATPIF1 knockout mice.

ABSTRACT: ATPIF1 (ATPase Inhibitory Factor 1) is a critical regulatory factor of mitochondrial ATP synthase, maintaining ATP homeostasis by modulating ATP synthesis and hydrolysis. In this study, we investigated the consequences of ATPIF1 knockout (KO) on terminal erythroid development and mitochondrial metabolic adaptation in mice. ATPIF1-KO mice exhibited significant reductions in peripheral red blood cell (RBC) counts, hemoglobin, and hematocrit. Mechanistic studies identified impaired development of bone marrow (BM) erythroid, accompanied by robust compensatory erythroid development in the spleen. Integrated RNA-seq and metabolomic analyses revealed that ATPIF1 deficiency disrupted cell proliferation and mitochondrial function in oxidative phosphorylation (OXPHOS) and the tricarboxylic acid (TCA

SUBMITTER: Feng J 

PROVIDER: S-EPMC12575250 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature