Related Experiment Video

Updated: Oct 20, 2025

Author Spotlight: Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals
05:59

Author Spotlight: Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals

Published on: May 19, 2023

3.1K

Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition

Kaori Saito1, Qi Zhang2, Haeun Yang1

  • 1Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Blood Advances
|September 10, 2021
PubMed

Insights

Acute myeloid leukemia (AML) cells resist oxidative phosphorylation (OxPhos) inhibition by acquiring mitochondria from bone marrow stromal cells. This mitochondrial transfer and internal adaptation help leukemia cells survive in the bone marrow microenvironment.

Area of Science:

  • Cancer Biology
  • Cellular Metabolism
  • Hematology

Background:

  • Acute myeloid leukemia (AML) cells rely heavily on oxidative phosphorylation (OxPhos) for energy.
  • The bone marrow (BM) microenvironment presents nutrient and oxygen fluctuations that AML cells must adapt to.
  • Understanding AML cell adaptation to metabolic stress is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate how the bone marrow microenvironment influences AML cell response to OxPhos inhibition.
  • To elucidate the mechanisms by which AML cells adapt to metabolic stress induced by OxPhos inhibition within the BM microenvironment.

Main Methods:

  • Utilized a novel complex I OxPhos inhibitor (IACS-010759) in co-culture models of AML and bone marrow stromal cells (mesenchymal stem cells - MSCs).
  • Performed cellular adhesion, growth, and apoptosis assays.
  • Measured mitochondrial DNA expression, mitochondrial reactive oxygen species (ROS) generation, and utilized electron microscopy for mitochondrial transport analysis.
  • Assessed the impact of cytarabine on mitochondrial transfer.

Main Results:

  • Direct contact with BM stromal cells induced compensatory mitochondrial respiration and resistance to OxPhos inhibition in AML cells.
  • OxPhos inhibition triggered transfer of functional mitochondria from MSCs to AML cells via tunneling nanotubes.
  • AML cells exhibited increased mitochondrial fission, functional mitochondria, and mitophagy in response to OxPhos inhibition.
  • The chemotherapy agent cytarabine enhanced MSC-to-AML cell mitochondrial transfer under OxPhos inhibition.

Conclusions:

  • Exogenous mitochondrial trafficking from BM stromal cells to AML cells is a key adaptation mechanism.
  • Endogenous mitochondrial fission and mitophagy also play significant roles in AML cell adaptation to energetic stress.
  • These findings highlight novel therapeutic strategies targeting metabolic vulnerabilities and intercellular communication in AML.

More Related Videos

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model06:05

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Published on: March 9, 2022

4.0K
MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells11:13

MitoCeption: Transferring Isolated Human MSC Mitochondria to Glioblastoma Stem Cells

Published on: February 22, 2017

13.2K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
15.4K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
8.5K
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
18.2K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
13.1K
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
8.3K
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
15.8K