Mitochondrial protease Afg3l2 regulates the homeostasis of mouse hematopoietic stem and progenitor cells through Mmadhc [RNA-Seq]

In order to study how mitochondrial proteases function on mouse hematopoietic stem cells, the article constructed Afg3l2 knockout mice. When Afg3l2 was knocked out, mouse hematopoietic stem cells showed HSC depletion accompanied by amino acid accumulation and TCA overactivation. We performed transcriptome and proteome sequencing analysis on cells from wild-type (WT) and Afg3l2-KO mice, and differential gene analysis revealed the Mmadhc protein. Further verification showed that Mmadhc is a substrate of the mitochondrial protease Afg3l2, and overexpression of Mmadhc can mimic the amino acid accumulation and TCA overactivation caused by Afg3l2 knockout. Overall, the mitochondrial protease Afg3l2 affects the homeostasis of hematopoietic stem cells by regulating the level of Mmadhc. Overall design: Comparative gene expression profiling was performed using RNA-seq data from WT and Afg3l2 KO LSK(Lin-Sca-1+c-Kit+) cells.