Related Experiment Video
Updated: May 20, 2026
Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
Rationale for mitochondria-targeting strategies in cancer bioenergetic therapies
Caroline Jose1, Rodrigue Rossignol
1Univ. Bordeaux, Maladies Rares: Génétique et Métabolisme (MRGM), EA 4576, F-33000 Bordeaux, France.
Abstract:
In the 1920s, Otto Warburg first hypothesized that mitochondrial impairment is a leading cause of cancer although he recognized the existence of oxidative tumors. Likewise, Weinhouse and others in the 50s found that deficient mitochondrial respiration is not an obligatory feature of cancer and Peter Vaupel suggested in the 1990s that tumor oxygenation rather than OXPHOS capacity was the limiting factor of mitochondrial energy production in cancer. Recent studies now clearly indicate that mitochondria are highly functional in mice tumors and the field of oncobioenergetic identified MYC, Oct1 and RAS as pro-OXPHOS oncogenes. In addition, cancer cells adaptation to aglycemia, metabolic symbiosis between hypoxic and non-hypoxic tumor regions as well the reverse Warburg hypothesis support the crucial role of mitochondria in the survival of a subclass of tumors. Therefore, mitochondria are now considered as potential targets for anti-cancer therapy and tentative strategies including a bioenergetic profile characterization of the tumor and the subsequent adapted bioenergetic modulation could be considered for cancer killing. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
Insights
Mitochondria are crucial for cancer survival, challenging early theories. Recent research highlights their functionality and role in tumor energy production, suggesting them as therapeutic targets.
Area of Science:
- Oncology
- Cellular Metabolism
- Cancer Bioenergetics
Background:
- Early cancer research (Warburg hypothesis) suggested mitochondrial dysfunction causes cancer.
- Subsequent studies indicated mitochondrial respiration is not always deficient in tumors.
- Recent findings reveal functional mitochondria in tumors, with oncogenes promoting oxidative phosphorylation (OXPHOS).
Purpose of the Study:
- To review the evolving understanding of mitochondria's role in cancer.
- To highlight evidence supporting mitochondria's crucial function in certain tumor types.
- To explore mitochondria as potential targets for anti-cancer therapies.
Main Methods:
- Historical review of cancer bioenergetics research.
- Synthesis of recent findings on mitochondrial function in tumors.
- Discussion of oncogenes influencing oxidative phosphorylation (OXPHOS).
Main Results:
- Mitochondria are highly functional in many tumors, contrary to initial hypotheses.
- Oncogenes like MYC, Oct1, and RAS promote oxidative phosphorylation (OXPHOS).
- Tumor adaptation, metabolic symbiosis, and the reverse Warburg effect underscore mitochondrial importance.
Conclusions:
- Mitochondria play a critical role in the survival of a subset of tumors.
- Targeting mitochondrial bioenergetics presents a promising avenue for anti-cancer therapy.
- Personalized therapeutic strategies may involve characterizing and modulating tumor bioenergetics.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:45Mitochondrial Membranes