Abstract

mtDNA deletions occur and accumulate preferentially in postmitotic, respiratory neurons and myofibers with age, and are associated with enzyme deficiencies and increased risk for cell death. The broad, long-term objectives of this application are to understand the mechanism of pathophysiology of mtDNA deletion mutations, and to what extent these mutations contribute to age-related deficits of function and atrophy of myofibers and neurons. The creation of cell lines bearing mtDNA deletions, differentiable into neurons and myotubes, is proposed, followed by the testing of the underlying mechanism by which mtDNA deletions are selected for, and the mechanism by which COX activity is decreased in mutant cells, and whether such deletions increase the risk for cell death.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG011967-13
Application #
6784517
Study Section
Special Emphasis Panel (ZRG1-MDCN-2 (01))
Program Officer
Finkelstein, David B
Project Start
1993-05-15
Project End
2007-06-30
Budget Start
2004-07-15
Budget End
2007-06-30
Support Year
13
Fiscal Year
2004
Total Cost
$252,532
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Shan, Yuxi; Cortopassi, Gino (2016) Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-sulfur cluster assembly. Mitochondrion 26:94-103
Schoenfeld, Robert; Wong, Alice; Silva, Jillian et al. (2010) Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation. Mitochondrion 10:143-50
Rolo, Anabela P; Palmeira, Carlos M; Cortopassi, Gino A (2009) Biosensor plates detect mitochondrial physiological regulators and mutations in vivo. Anal Biochem 385:176-8
Lu, Chunye; Schoenfeld, Robert; Shan, Yuxi et al. (2009) Frataxin deficiency induces Schwann cell inflammation and death. Biochim Biophys Acta 1792:1052-61
Silva, Jillian M; Wong, Alice; Carelli, Valerio et al. (2009) Inhibition of mitochondrial function induces an integrated stress response in oligodendroglia. Neurobiol Dis 34:357-65
Napoli, Eleonora; Morin, Dexter; Bernhardt, Rita et al. (2007) Hemin rescues adrenodoxin, heme a and cytochrome oxidase activity in frataxin-deficient oligodendroglioma cells. Biochim Biophys Acta 1772:773-80
Prigione, Alessandro; Cortopassi, Gino (2007) Mitochondrial DNA deletions induce the adenosine monophosphate-activated protein kinase energy stress pathway and result in decreased secretion of some proteins. Aging Cell 6:619-30
Alemi, Mansour; Prigione, Alessandro; Wong, Alice et al. (2007) Mitochondrial DNA deletions inhibit proteasomal activity and stimulate an autophagic transcript. Free Radic Biol Med 42:32-43
Lu, Chunye; Cortopassi, Gino (2007) Frataxin knockdown causes loss of cytoplasmic iron-sulfur cluster functions, redox alterations and induction of heme transcripts. Arch Biochem Biophys 457:111-22
Shan, Yuxi; Napoli, Eleonora; Cortopassi, Gino (2007) Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet 16:929-41

Showing the most recent 10 out of 35 publications