Electron Transport Complex IV

Publication Title: 
Mutation Research

During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse.

Melov, S.
Coskun, P. E.
Wallace, D. C.
Publication Title: 

P. anserina mutants with impairments in complex IV (COX) of the respiratory chain are characterized by an increase in lifespan. Examples are the nuclear grisea mutant with a moderate lifespan extension (60%) and the immortal extranuclear ex1 mutant. Here we report data demonstrating that in mutant ex1 the level of the alternative oxidase (PaAOX) is significantly higher than in mutant grisea. PaAOX levels appear to be reversely dependent on COX activity.

Borghouts, Corina
Scheckhuber, Christian Q.
Werner, Alexandra
Osiewacz, Heinz D.
Publication Title: 
Journal of Theoretical Biology

The mitochondrial theory of ageing is one of the main contenders to explain the biochemical basis of the ageing process. An important line of support comes from the observation that mtDNA deletions accumulate over the life course in post-mitotic cells of many species. A single mutant expands clonally and finally replaces the wild-type population of a whole cell. One proposal to explain the driving force behind this accumulation states that the reduced size leads to a shorter replication time, which provides a selection advantage.

Kowald, Axel
Dawson, Marcus
Kirkwood, Thomas B. L.
Publication Title: 
PloS One

Caloric restriction (CR) extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS) that shows increased free radical production.

Patel, Barkha P.
Safdar, Adeel
Raha, Sandeep
Tarnopolsky, Mark A.
Hamadeh, Mazen J.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Recent work shows that S-adenosylmethionine (AdoMet) helps maintain normal liver function as chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. The mechanisms by which these nontraditional functions of AdoMet occur are unknown. Here, we use knockout mice deficient in hepatic AdoMet synthesis (MAT1A(-/-)) to study the proteome of the liver during the development of steatohepatitis.

Santamaría, Enrique
Avila, Matías A.
Latasa, M. Ujue
Rubio, Angel
Martín-Duce, Antonio
Lu, Shelly C.
Mato, José M.
Corrales, Fernando J.
Publication Title: 

Parkinson's disease is a common progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Mitochondrial dysfunction has been strongly implicated in the pathogenesis of Parkinson's disease. Thus, therapeutic approaches that improve mitochondrial function may prove to be beneficial.

Liang, H. L.
Whelan, H. T.
Eells, J. T.
Wong-Riley, M. T. T.
Publication Title: 
Investigative Ophthalmology & Visual Science

PURPOSE: Mutations in ANT, a mitochondrial ATP transporter, are typically associated with myopathy. Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology. METHODS: RT-PCR was used to confirm Ant1 expression in retinas of wild-type (WT) or Ant1(-/-) mice. Full-field ERGs were used to test retinal function under dark- and light-adapted conditions and the recovery of the photoresponse to a bright flash.

Phillips, M. Joseph
Webb-Wood, Sarah
Faulkner, Amanda E.
Jabbar, Seema B.
Biousse, Valerie
Newman, Nancy J.
Do, Vi T.
Boatright, Jeffrey H.
Wallace, Douglas C.
Pardue, Machelle T.
Publication Title: 
Journal of Alzheimer's disease: JAD

Alzheimer's disease (AD) causes progressive, age-dependent cortical and hippocampal dysfunction leading to abnormal intellectual capacity and memory. We propose a novel protective treatment for AD pathology with phytic acid (inositol hexakisphosphate), a phytochemical found in food grains and a key signaling molecule in mammalian cells. We evaluated the protective and beneficial effects of phytic acid against amyloid-β (Aβ) pathology in MC65 cells and the Tg2576 mouse model.

Anekonda, Thimmappa S.
Wadsworth, Teri L.
Sabin, Robert
Frahler, Kate
Harris, Christopher
Petriko, Babett
Ralle, Martina
Woltjer, Randy
Quinn, Joseph F.
Publication Title: 
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology

Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species.

Shi, Yun
Pulliam, Daniel A.
Liu, Yuhong
Hamilton, Ryan T.
Jernigan, Amanda L.
Bhattacharya, Arunabh
Sloane, Lauren B.
Qi, Wenbo
Chaudhuri, Asish
Buffenstein, Rochelle
Ungvari, Zoltan
Austad, Steven N.
Van Remmen, Holly
Publication Title: 
Science Translational Medicine

Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage.

Crane, Justin D.
Ogborn, Daniel I.
Cupido, Colleen
Melov, Simon
Hubbard, Alan
Bourgeois, Jacqueline M.
Tarnopolsky, Mark A.


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