Send to

Choose Destination
Am J Pathol. 2008 Jun;172(6):1445-56. doi: 10.2353/ajpath.2008.071163. Epub 2008 May 5.

Expression and maintenance of mitochondrial DNA: new insights into human disease pathology.

Author information

Departments of Pathology and Genetics, Yale University School of Medicine, 310 Cedar St., P.O. Box 208023, New Haven, CT 06520-8023.


Mitochondria are central players in cellular energy metabolism and, consequently, defects in their function result in many characterized metabolic diseases. Critical for their function is mitochondrial DNA (mtDNA), which encodes subunits of the oxidative phosphorylation complexes essential for cellular respiration and ATP production. Expression, replication, and maintenance of mtDNA require factors encoded by nuclear genes. These include not only the primary machinery involved (eg, transcription and replication components) but also those in signaling pathways that mediate or sense alterations in mitochondrial function in accord with changing cellular needs or environmental conditions. Mutations in these contribute to human disease pathology by mechanisms that are being revealed at an unprecedented rate. As I will discuss herein, the basic protein machinery required for transcription initiation in human mitochondria has been elucidated after the discovery of two multifunctional mitochondrial transcription factors, h-mtTFB1 and h-mtTFB2, that are also rRNA methyltransferases. In addition, involvement of the ataxia-telangiectasia mutated (ATM) and target of rapamycin (TOR) signaling pathways in regulating mitochondrial homeostasis and gene expression has also recently been uncovered. These advancements embody the current mitochondrial research landscape, which can be described as exploding with discoveries of previously unanticipated roles for mitochondria in human disease and aging.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center