Genomes and Genes
Experts and Doctors on mitochondria in Novato, California, United States
Locale: Novato, California, United States
- Flynn J, Melov S. SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radic Biol Med. 2013;62:4-12 pubmed publisher..We also examine in vivo models of endogenous oxidative damage based upon the loss of SOD2 and associated neurological phenotypes in relation to human neurodegenerative disorders. ..
- Nicholls D. Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Curr Mol Med. 2004;4:149-77 pubmed
- Rego A, Vesce S, Nicholls D. The mechanism of mitochondrial membrane potential retention following release of cytochrome c in apoptotic GT1-7 neural cells. Cell Death Differ. 2001;8:995-1003 pubmed..These results indicate that the maintenance of Delta Psi(M) following release of cyt c may be a consequence of ATP synthase reversal and cytoplasmic ATP hydrolysis in STS-treated GT1-7 cells. ..
- Wiley C, Velarde M, Lecot P, Liu S, Sarnoski E, Freund A, et al. Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab. 2016;23:303-14 pubmed publisher..Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes. ..
- Orr A, Quinlan C, Perevoshchikova I, Brand M. A refined analysis of superoxide production by mitochondrial sn-glycerol 3-phosphate dehydrogenase. J Biol Chem. 2012;287:42921-35 pubmed publisher..These results clarify the maximum rate and mechanism of superoxide production by mGPDH. ..
- Melov S, Adlard P, Morten K, Johnson F, Golden T, Hinerfeld D, et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE. 2007;2:e536 pubmed..These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD. ..
- Miller J, Yates B, Al Ramahi I, Berman A, Sanhueza M, Kim E, et al. A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease. PLoS Genet. 2012;8:e1003042 pubmed publisher..These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease. ..
- Flynn J, Czerwieniec G, Choi S, Day N, Gibson B, Hubbard A, et al. Proteogenomics of synaptosomal mitochondrial oxidative stress. Free Radic Biol Med. 2012;53:1048-60 pubmed publisher..As a result of using these approaches, we report for the first time an activation of the mTOR pathway in synaptosomes isolated from Sod2 null mice, confirmed by an upregulation of the phosphorylation of 4E-BP1. ..
- Peters T, Miller A, Tourette C, Agren H, Hubbard A, Hughes R. Genomic Analysis of ATP Efflux in Saccharomyces cerevisiae. G3 (Bethesda). 2015;6:161-70 pubmed publisher..These results will facilitate analysis of ATP efflux mechanisms in higher eukaryotes. ..
- Velarde M, Flynn J, Day N, Melov S, Campisi J. Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin. Aging (Albany NY). 2012;4:3-12 pubmed..Our results support the idea that mitochondrial oxidative stress and cellular senescence contribute to aging skin phenotypes in vivo. ..
- Viswanath V, Wu Y, Boonplueang R, Chen S, Stevenson F, Yantiri F, et al. Caspase-9 activation results in downstream caspase-8 activation and bid cleavage in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease. J Neurosci. 2001;21:9519-28 pubmed..These data suggest that caspase inhibitors constitute a plausible therapeutic for PD. ..
- Brand M, Nicholls D. Assessing mitochondrial dysfunction in cells. Biochem J. 2011;435:297-312 pubmed publisher..Many other measurements in current use can be more problematic, as discussed in the present review. ..
- Melov S, Doctrow S, Schneider J, Haberson J, Patel M, Coskun P, et al. Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J Neurosci. 2001;21:8348-53 pubmed
- Danielson S, Held J, Oo M, Riley R, Gibson B, Andersen J. Quantitative mapping of reversible mitochondrial Complex I cysteine oxidation in a Parkinson disease mouse model. J Biol Chem. 2011;286:7601-8 pubmed publisher..Three of these residues were found to reside within iron-sulfur clusters of Complex I, suggesting that their redox state may affect electron transport function. ..
- Nicholls D. Simultaneous monitoring of ionophore- and inhibitor-mediated plasma and mitochondrial membrane potential changes in cultured neurons. J Biol Chem. 2006;281:14864-74 pubmed..ATP synthase reversal following respiratory chain inhibition depolarizes the mitochondria by 26 mV. ..
- Lee D, Kaur D, Chinta S, Rajagopalan S, Andersen J. A disruption in iron-sulfur center biogenesis via inhibition of mitochondrial dithiol glutaredoxin 2 may contribute to mitochondrial and cellular iron dysregulation in mammalian glutathione-depleted dopaminergic cells: implications for Parkinson's di. Antioxid Redox Signal. 2009;11:2083-94 pubmed publisher..This suggests that glutathione depletion may affect important pathologic cellular events associated with PD through its effects on Grx2 activity and mitochondrial Fe-S biogenesis. ..
- Chinta S, Rane A, Yadava N, Andersen J, Nicholls D, Polster B. Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radic Biol Med. 2009;46:939-47 pubmed..These findings raise the important possibility that complex I contributes less to physiological ROS production by brain mitochondria than previously suggested. ..
- Samper E, Morgado L, Estrada J, Bernad A, Hubbard A, Cadenas S, et al. Increase in mitochondrial biogenesis, oxidative stress, and glycolysis in murine lymphomas. Free Radic Biol Med. 2009;46:387-96 pubmed publisher..Understanding these adaptations is likely to result in improved therapeutic strategies for this tumor type. ..
- Johnson Cadwell L, Jekabsons M, Wang A, Polster B, Nicholls D. 'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J Neurochem. 2007;101:1619-31 pubmed..It is concluded that the 'mild uncoupling' hypothesis is not supported by this model. ..
- Hinerfeld D, Traini M, Weinberger R, Cochran B, Doctrow S, Harry J, et al. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem. 2004;88:657-67 pubmed..In addition, we observed a striking pattern of neuronal cell death as a result of mitochondrial oxidative stress, and were able to significantly reduce the loss of neurons via antioxidant treatment. ..
- del Rio G, Castro Obregon S, Rao R, Ellerby H, Bredesen D. APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide. FEBS Lett. 2001;494:213-9 pubmed..Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy. ..
- Polster B, Basañez G, Etxebarria A, Hardwick J, Nicholls D. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem. 2005;280:6447-54 pubmed..Taken together, these results define a novel mechanism of AIF release involving calpain processing and identify a potential molecular checkpoint for cytoprotective interventions. ..
- Golden T, Hubbard A, Morten K, Hinerfeld D, Melov S. Pharmacogenomic profiling of an oxidative stress-mediated spongiform encephalopathy. Free Radic Biol Med. 2005;39:152-63 pubmed..The normalization of expression of some of these pathways by antioxidant treatment suggests approaches to treating disease in which endogenous oxidative stress plays a role. ..
- Siddiqui A, Chinta S, Mallajosyula J, Rajagopolan S, Hanson I, Rane A, et al. Selective binding of nuclear alpha-synuclein to the PGC1alpha promoter under conditions of oxidative stress may contribute to losses in mitochondrial function: implications for Parkinson's disease. Free Radic Biol Med. 2012;53:993-1003 pubmed publisher..This represents a novel role for alpha-synuclein as it relates to mitochondrial dysfunction in PD. ..
- Quinlan C, Orr A, Perevoshchikova I, Treberg J, ACKRELL B, Brand M. Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions. J Biol Chem. 2012;287:27255-64 pubmed publisher..We suggest that complex II may be an important contributor to physiological and pathological ROS production. ..
- Vesce S, Jekabsons M, Johnson Cadwell L, Nicholls D. Acute glutathione depletion restricts mitochondrial ATP export in cerebellar granule neurons. J Biol Chem. 2005;280:38720-8 pubmed..The initial bioenergetic consequence of neuronal GSH depletion in this model is thus an inhibition of ATP export, which precedes other forms of mitochondrial dysfunction. ..
- Morten K, Ackrell B, Melov S. Mitochondrial reactive oxygen species in mice lacking superoxide dismutase 2: attenuation via antioxidant treatment. J Biol Chem. 2006;281:3354-9 pubmed..Increased production of O2* resulting from complex II normalization had no effect on steady state levels due to the rapid conversion to H2O2, a process presumably aided by the presence of the EUK189, an SOD mimetic...
- Choi S, Gerencser A, Lee D, Rajagopalan S, Nicholls D, Andersen J, et al. Intrinsic bioenergetic properties and stress sensitivity of dopaminergic synaptosomes. J Neurosci. 2011;31:4524-34 pubmed publisher..We conclude that the intrinsic bioenergetic capacities of dopaminergic and nondopaminergic presynaptic synaptosomes from mice do not differ...