Related Experiment Video

Updated: Nov 8, 2025

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

2.6K

Asparagine, a Key Metabolite in Cellular Response to Mitochondrial Dysfunction

Yuyang Liu1, Kıvanç Birsoy1

  • 1Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

Trends in Cancer
|April 26, 2021
PubMed

Insights

Targeting the mitochondrial electron transport chain (ETC) in cancer is promising. Researchers found that limiting asparagine under ETC dysfunction halts cancer cell growth and creates a therapeutic vulnerability.

Area of Science:

  • Oncology
  • Metabolic pathways
  • Mitochondrial function

Background:

  • The mitochondrial electron transport chain (ETC) is crucial for tumor growth and proliferation.
  • The ETC is a validated target for anti-cancer drug development.
  • Metabolic reprogramming is a hallmark of cancer, offering therapeutic opportunities.

Purpose of the Study:

  • To investigate the metabolic consequences of ETC dysfunction in cancer cells.
  • To identify specific metabolic vulnerabilities exploitable for cancer therapy.
  • To understand the role of amino acid metabolism in response to ETC inhibition.

Main Methods:

  • Utilized cancer cell models with induced ETC dysfunction.
  • Performed metabolic profiling to assess changes in amino acid levels.
  • Analyzed the integrated stress response activation.
  • Evaluated the impact of asparagine levels on cancer cell proliferation.

Main Results:

  • ETC dysfunction led to a significant decrease in intracellular asparagine levels.
  • Reduced asparagine availability was found to limit cancer cell proliferation.
  • Asparagine depletion triggered the integrated stress response.
  • These findings highlight a specific metabolic vulnerability associated with ETC dysfunction.

Conclusions:

  • Targeting the mitochondrial ETC creates a metabolic vulnerability related to asparagine.
  • Asparagine limitation is a key factor in controlling cancer cell proliferation under ETC stress.
  • The integrated stress response is activated upon asparagine depletion, suggesting a feedback mechanism.
  • This metabolic vulnerability presents a potential therapeutic strategy for cancer treatment.

More Related Videos

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

15.2K
Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts06:32

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts

Published on: April 13, 2022

1.9K

Related Concept Videos

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,...
17.2K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
15.7K
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,...
9.7K
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,...
14.4K
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...
16.5K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.1K