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Letters Funding/Support: This work was supported by grants MH108592, NS021328, aspect of cellular metabolism, regulates nDNA gene expres- CA182384, and DO10944 awarded to Dr Wallace from the National Institutes of sion through the epigenome, and must be coordinated with Health. the nucleus-cytosol by a complex array of regulatory net- 1. Chalkia D, Singh LN, Leipzig J, et al. Association between mitochondrial DNA works. The mtDNA codes for the central proteins of mitochon- haplogroup variation and autism spectrum disorders. JAMA Psychiatry. 2017;74 drial oxidative phosphorylation, which is sensitive to envi- (11):1161-1168. ronmental agents and insults. Hence, only the most severe 2. Wang Y, Picard M, Gu Z. Genetic evidence for elevated pathogenicity of mitochondrial DNA heteroplasmy in autism spectrum disorder. PLoS Genet. mitochondrial gene defects act alone to cause a clinical 2016;12(10):e1006391. phenotype. 3. Picard M, Zhang J, Hancock S, et al. Progressive increase in mtDNA 3243A>G Systemic mitochondrial dysfunction commonly affects heteroplasmy causes abrupt transcriptional reprogramming. Proc Natl Acad Sci the high energy demand brain, but other energy-intensive USA. 2014;111(38):e4033-e4042. organs can also be impaired. Kozicz et al argue that because 4. Anglin RE, Tarnopolsky MA, Mazurek MF, Rosebush PI. The psychiatric Leu(UUR) the tRNA 3243A>G mutation manifests as
JAMA Psychiatry – American Medical Association
Published: May 4, 2018
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