Mitochondria in human acute myeloid leukemia cell lines have ultrastructural alterations linked to deregulation of their respiratory profiles

•The presence of MAMs and matrix granules in AML cell lines is evidence that there are active communication processes between endoplasmic reticulum mitochondria AML. •HL60 carrying high levels favor conserved has a higher sensitivity to drugs targeting (rotenone/antimycin). •Conversely, K562, the ASXL1 mutation, exhibits decrease numbers granules, MAM, MDV precursors associated with chemoresistance mitochondria. •Through transcriptomic analysis, we confirm implication mutation mitochondria–ER contact deficiency, thereby providing potential explanation worse prognostic value mutation. Mitochondria not only essential for metabolism energy supply but also engaged calcium homeostasis reactive oxygen species generation play key role apoptosis. As consequence, functional mitochondrial disorders involved many human cancers including acute myeloid leukemia (AML). However, very few data available on deregulation their number and/or shape leukemic cells, despite evident link ultrastructure function. In this context, analyzed ultrastructural parameters (number per cell, area, cristae/mitochondria, cristal thickness) five (HEL, HL60, KG1, OCI-AML3) together assay respiratory profile. First, describe significant differences basal respiration, maximal ATP production, spare capacity our lines, confirming various profiles among subtypes. Second, highlight these variations obviously interleukemia heterogeneity For instance, characterized by smallest reduced diameter, had particularly deficient comparison, HEL K562 both profiles, harbored largest mitochondria/cells diameters. Moreover, report presents mitochondria–endoplasmic deficiency reflected decreases mitochondria-associated membrane (MAM) mitochondrial-derived vesicle (MDV) precursors, which implicated regulatory pathways mortality via mitophagy homeostasis. Contrarily, HL60 carried We dysregulation through study transcript expression (from 415 patients public data) three pathways: (1) reticulum–mitochondria contacts (MAMs), (2) granule homeostasis, (3) precursor production. Our offers new original structural alterations linked respiration AMLs some genetic characteristics, suggesting modifications cells participate could be targeted mechanism regulate proliferative potential.