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Mitochondria: more than mitochondrial DNA in cancer

Posted by plosmedicine on 30 Mar 2009 at 23:49 GMT

Author: Bora Baysal
Position: MD, Ph.D Assistant Professor
Institution: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA, 15213
Submitted Date: December 29, 2005
Published Date: January 5, 2006
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

In their article entitled 'A critical reassessment of the role of mitochondria in tumorigenesis' in PLoS Med 2: 2005 Oct 4;2(11):e296, Salas et al [1]. reviewed reports describing identification of mitochondrial DNA (mtDNA) mutations in several tumors. They identified many instances where the purported mutations in tumors corresponded to certain populational haplotypes, suggesting that contamination or sample mix-up could be a better explanation for these mtDNA variations found in tumors. This manuscript has important implications for this research field by questioning the validity of conclusions drawn in several high profile publications that laid foundations for role of mitochondrial DNA in cancer. While it is essential to investigate the origin of mtDNA variations found in certain tumors, the conclusion in the abstract that 'The role of mitochondria in tumorigenesis remains unclarified' is simply incorrect.

The causal link between mitochondrial abnormalities and tumorigenesis is provided by the positional cloning of the hereditary paraganglioma gene at chromosome band 11q23 as the SDHD subunit gene of mitochondrial complex II (succinate dehydrogenase) in year 2000 [2]. Since then, the role of mitochondria in cancer is further highlighted through identification of over 100 mutations in the SDHB, SDHC and SDHD subunit genes in hundreds of index cases and families with hereditary and sporadic paragangliomas and pheochromocytomas [3]. Furthermore, fumarase gene mutations in a distinct hereditary tumor syndrome characterized by multiple skin and uterine leiomyomatosis and renal cell cancer (HLRCC) further strengthened the role of mitochondria in cancer [4].

Although it is clear that Salas et al. question specifically the mutations in mtDNA of tumors, they did not acknowledge the causal link between mitochondria and cancer provided by the discovery of nuclear-encoded mitochondrial gene mutations. This is especially important because, in their unfortunate title and in their conclusion, the authors seem to make a sweeping statement against the role of mitochondria in cancer. It is essential to emphasize to readers that it is the mtDNA, but not mitochondria, with a questionable role in tumorigenesis.


[1] Salas A, Yao YG, Macaulay V, Vega A, Carracedo A et al. (2005) A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med 2: e296 DOI: 10.1371/journal.pmed.0020296.

[2] Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B. (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 287(5454):848-51

[3] Bayley JP, Devilee P, Taschner PE. (2005) The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet.6(1):39.

[4] Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomaki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA. (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 30(4):406-10.

Competing interests declared: I have no competing interests