Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming

Picard M, Zhang J, Hancock S, Derbeneva O, Golhar R, Golik P, O'Hearn S, Levy S, Potluri P, Lvova M, Davila A, Lin CS, Perin JC, Rappaport EF, Hakonarson H, Trounce IA, Procaccio V, Wallace DC. Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):E4033-42 | doi: 10.1073/pnas.1414028111


A new study by the Wallace Lab details how subtle changes in mitochondrial function may cause a broad range of common metabolic and degenerative diseases. Mitochondria are tiny energy-producing structures within cells that contain their own DNA. The study demonstrates that small changes in the ratio of mutant to normal mitochondrial DNA within the thousands of mitochondrial DNAs inside each cell can cause abrupt changes in the expression of numerous genes within the nuclear DNA. The findings challenge the traditional “single mutation–single disease” concept and provide an alternative perspective into understanding the underlying cause of metabolic and neurodegenerative disorders such as diabetes, Alzheimer, Parkinson and Huntington disease, cancer, and aging.

Read the CHOP Research Communications announcement