Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jul 15;1(2):129-139.
doi: 10.1002/mco2.16. eCollection 2020 Sep.

Mitochondria as a target in cancer treatment

Yu'e Liu  1 , Yufeng Shi  1   2
Affiliations
Review

Mitochondria as a target in cancer treatment

Yu'e Liu et al. MedComm (2020). .

Abstract

Mitochondria are biosynthetic, bioenergetic, and signaling organelles existing in almost all eukaryotic cells, and their dysregulated function has been proved to be essential for tumorigenesis, tumor development, and tumor metastasis. In this short review, first, we briefly summarize the historic misunderstanding of mitochondria in tumors, and then come up with a current view that mitochondria play a pivotal role in tumor cells; second, we review how tumor cells rewind mitochondrial function for their oncogenic purpose via known or unknown mechanisms by key oncogenes or tumor suppressors; third, we go through reagents and strategies currently available targeting mitochondria when treating tumors. Recently, merging data suggest that slow cycling cancer cells/cancer stem cells have distinctive mitochondrial metabolism comparing to bulk tumor cells and mitochondria inhibitors seem to be promising to target them, which are resistant to traditional radio and chemotherapies. We thus discuss role of mitochondria in these cancer stem cells and summarize mitochondria as a target from different aspects.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Role of mitochondria in tumor. Role of mitochondria in bioenergetics, cell death, biogenesis, signaling, and tumor microenvironment
FIGURE 2
FIGURE 2
Mitochondria reprogramming in tumor. Some oncoproteins or tumor suppressors function within mitochondria (such as IDH1/2, SDH, and FHs) generating oncogenic metabolites initiating tumor formation, and many others directly or indirectly affect mitochondrial function (mutations including but not limited to that in Pi3k/Akt /mTOR pathway, Tp53, and Myc) and reprograming mitochondria metabolism enabling tumor transformation
FIGURE 3
FIGURE 3
Molecule targeting the mitochondrial OXPHOS pathway. The OXPHOS pathway plays an essential role in mitochondria and tumorigenesis. Multiple small molecules have been developed to inhibit this pathway at several levels. Tigecycline inhibits translation of mitochondria mRNA into OXPHOS subunits; Gamitrinib inhibition OXPHOS assembly; Deguelin, metformin and IACS‐010759 inhibits complex I in the OXPHOS pathway, while Gboxin inhibits complex V
See this image and copyright information in PMC

References

    1. Ernster L, Schatz G. Mitochondria: a historical review. J Cell Biol. 1981;91(3 Pt 2):227s‐255s. - PMC - PubMed
    1. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309‐314. - PubMed
    1. Buescher JM, Antoniewicz MR, Boros LG, et al. A roadmap for interpreting (13)C metabolite labeling patterns from cells. Curr Opin Biotechnol. 2015;34:189‐201. - PMC - PubMed
    1. Tan AS, Baty JW, Dong LF, et al. Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab. 2015;21(1):81‐94. - PubMed
    1. Weinberg F, Hamanaka R, Wheaton WW, et al. Mitochondrial metabolism and ROS generation are essential for Kras‐mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010;107(19):8788‐8793. - PMC - PubMed