Experts and Doctors on mitochondria in Novato, California, United States


Locale: Novato, California, United States
Topic: mitochondria

Top Publications

  1. Wong H, Dighe P, Mezera V, Monternier P, Brand M. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem. 2017;292:16804-16809 pubmed publisher
  2. Chinta S, Andersen J. Nitrosylation and nitration of mitochondrial complex I in Parkinson's disease. Free Radic Res. 2011;45:53-8 pubmed publisher
    ..Strategies to modulate mitochondrial NO levels will therefore likely be a promising approach to enhance mitochondrial function and protect dopaminergic neurons against oxidative or nitrosative insult. ..
  3. Chalmers S, Nicholls D. The relationship between free and total calcium concentrations in the matrix of liver and brain mitochondria. J Biol Chem. 2003;278:19062-70 pubmed
    ..The solubility product of amorphous Ca3(PO4)2 is consistent with the observed matrix free calcium concentration, and the matrix pH is proposed to play the major role in maintaining the low matrix free calcium concentration. ..
  4. Choi S, Gerencser A, Ng R, Flynn J, Melov S, Danielson S, et al. No consistent bioenergetic defects in presynaptic nerve terminals isolated from mouse models of Alzheimer's disease. J Neurosci. 2012;32:16775-84 pubmed publisher
    ..Our results support the conclusion that the intrinsic bioenergetic capacities of presynaptic nerve terminals are maintained in these symptomatic AD mouse models. ..
  5. Mookerjee S, Brand M. Characteristics of the turnover of uncoupling protein 3 by the ubiquitin proteasome system in isolated mitochondria. Biochim Biophys Acta. 2011;1807:1474-81 pubmed publisher
    ..We propose that matrix ATP and a high membrane potential are needed for UCP3 to be polyubiquitylated through lysine-48 of ubiquitin and exported to the cytosolic 26S proteasome, where it is de-ubiquitylated and degraded. ..
  6. Nicholls D. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int J Biochem Cell Biol. 2002;34:1372-81 pubmed
    ..These interactions are incompletely understood and in this review I present an overview of some of the current research in this area, and its possible relevance to aging and aging-related disease. ..
  7. Chinta S, Andersen J. Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease. Free Radic Biol Med. 2006;41:1442-8 pubmed
  8. Quinlan C, Gerencser A, Treberg J, Brand M. The mechanism of superoxide production by the antimycin-inhibited mitochondrial Q-cycle. J Biol Chem. 2011;286:31361-72 pubmed publisher
    ..These mechanisms limit superoxide production and short circuiting of the Q-cycle when electron transfer slows. ..
  9. Bharat S, Cochran B, Hsu M, Liu J, Ames B, Andersen J. Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson's disease therapy. Neurotoxicology. 2002;23:479-86 pubmed
    ..Here we report that pre-treatment of PC12 cells with R-lipoic acid acts to prevent depletion of GSH content and preserves the mitochondrial complex I activity which normally is impaired as a consequence of GSH loss. ..

More Information


  1. 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. ..
  2. Gerencser A, Brand M. Exploiting Mitochondria In Vivo as Chemical Reaction Chambers Dependent on Membrane Potential. Mol Cell. 2016;61:642-643 pubmed publisher
  3. Nicholls D. Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Curr Mol Med. 2004;4:149-77 pubmed
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. 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. ..
  10. 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. ..
  11. 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. ..
  12. 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. ..
  13. 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. ..
  14. 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
  15. Treberg J, Quinlan C, Brand M. Evidence for two sites of superoxide production by mitochondrial NADH-ubiquinone oxidoreductase (complex I). J Biol Chem. 2011;286:27103-10 pubmed publisher
  16. Flynn J, Choi S, Day N, Gerencser A, Hubbard A, Melov S. Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice. Free Radic Biol Med. 2011;50:866-73 pubmed publisher
  17. 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. ..
  18. 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. ..
  19. Brand M. The sites and topology of mitochondrial superoxide production. Exp Gerontol. 2010;45:466-72 pubmed publisher
  20. Choi S, Gerencser A, Nicholls D. Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure. J Neurochem. 2009;109:1179-91 pubmed publisher
  21. 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. ..
  22. 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. ..
  23. Nicholls D. Oxidative stress and energy crises in neuronal dysfunction. Ann N Y Acad Sci. 2008;1147:53-60 pubmed publisher
  24. 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. ..
  25. 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. ..
  26. Schwarzlander M, Wagner S, Ermakova Y, Belousov V, Radi R, Beckman J, et al. The 'mitoflash' probe cpYFP does not respond to superoxide. Nature. 2014;514:E12-4 pubmed publisher
  27. 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. ..
  28. 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. ..
  29. 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. ..
  30. 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. ..
  31. Siddiqui A, Rivera Sánchez S, Castro M, Acevedo Torres K, Rane A, Torres Ramos C, et al. Mitochondrial DNA damage is associated with reduced mitochondrial bioenergetics in Huntington's disease. Free Radic Biol Med. 2012;53:1478-88 pubmed publisher
  32. 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. ..
  33. 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. ..
  34. 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. ..
  35. 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...
  36. 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...