Mitochondrial DNA mutations in cancer

Abstract

One can no longer ignore mitochondria in cancer biology, argue Zanssen and Schon.

Figure 1. Schematic Model for Tumorigenesis in SDH deficiency

SDH is a component of the OxPhos complexes (I–IV) as well as the TCA cycle. Due to SDH deficiency succinate accumulates intramitochondrially (the same occurs when FH is deficient) and is transported into the cytosol. Here, its elevated concentration inhibits prolyl hydroxylases (PDH1-3), which can no longer degrade HIF-1α even under normoxic conditions. Heterodimerisation of stabilized HIF-1α and HIF-1β now forms HIF, which induces transcription of nuclear genes involved in tumor progression [5]. (Illustration: Giovanni Maki)

Figure 2. Mutations C12308T and T12372C Alter Polymorphisms Specifying European Mitochondrial Haplotype U

Mutation load in (A) MDS, (B) MDS in transformation, and (C) acute leukemia.