Mitochondrial dynamics as a pathobiological mediator of clonal myeloid disorders.

Abstract

Myeloid malignancies, including myelodysplastic syndromes and acute myeloid leukemia, are a group of clonal hematopoietic stem cell (HSC) diseases. The incidence increases with global population aging. Genome sequencing uncovered mutational profiles in patients with myeloid malignancies and healthy elderly individuals. However, the molecular and cellular basis of disease development remains unclear. Accumulating evidence shows mitochondrial involvement in the pathogenesis of myeloid malignancies, aging-related HSC phenotypes, and clonal hematopoiesis. Mitochondria are dynamic organelles that continuously undergo fission and fusion processes to maintain their function, integrity, and activity. Mitochondria could be a hub of various biological processes that underlie cellular and systemic homeostasis. Thus, mitochondrial dysfunction could directly lead to the disruption of cellular homeostasis and the development of various disorders, including cancer. Notably, emerging data have revealed that mitochondria dynamics also primarily affect not only mitochondrial function and activity but also cellular homeostasis, the aging process, and tumorigenesis. Here, by focusing on mitochondrial dynamics, we highlight the current understanding of mitochondrial roles as a pathobiological mediator of myeloid malignancies and aging-related clonal hematopoiesis.