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

• DOI: 10.1073/pnas.1414028111
• Publication Date: 2014-09-06T07:25:27Z
• Authors: Martin Picard; Jiangwen Zhang; Saege Hancock; Olga Derbeneva; Ryan Golhar; Pawel Golik; Sean O’Hearn; Shawn Levy; Prasanth Potluri; Maria Lvova; Antonio Davila; Chun Shi Lin; Juan Carlos Perin; Eric F. Rappaport; Hakon Hakonarson; Ian A. Trounce; Vincent Procaccio; Douglas C. Wallace
• Keywords: Heteroplasmy; Mitochondrial disease

Significance Mitochondria generate signals that regulate nuclear gene expression via retrograde signaling, but this phenomenon is rendered more complex by the quantitative differences in percentage of mutant and normal mtDNAs can exist within patient cells. This study demonstrates depending upon its relative cytoplasmic levels, a single mtDNA point mutation cause discrete set cellular transcriptional responses cells same background. qualitative regulation changes levels challenges traditional “single mutation–single disease” concept provides an alternative perspective on molecular basis metabolic degenerative diseases, cancer, aging.