References 1. Schiesling C, Kieper N, Seidel K, Kruger R (2008) Review: Familial Parkinson’s disease–genetics, clinical phenotype and neuropathology in relation to the common sporadic form of the disease. Neuropathol Appl Neurobiol 34: 255–271. 2. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, et al. (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304: 1158–1160. 3. Strauss KM, Martins LM, Plun-Favreau H, Marx FP, Kautzmann S, et al. (2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson’s disease. Hum Mol Genet 14: 2099–2111. 4. Schapira AH (2008) Mitochondrial dysfunction in neurodegenerative diseases. Neurochem Res 33: 2502–2509. 5. Bonifati V, Rizzu P, Squitieri F, Krieger E, Vanacore N, et al. (2003) DJ- 1(PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol Sci 24: 159–160. 6. Klein C, Lohmann-Hedrich K (2007) Impact of recent genetic findings in Parkinson’s disease. Curr Opin Neurol 20: 453–464. 7. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, et al. (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299: 256–259. 8. Hering R, Strauss KM, Tao X, Bauer A, Woitalla D, et al. (2004) Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Hum Mutat 24: 321–329. 9. Cookson MR (2003) Pathways to Parkinsonism. Neuron 37: 7–10. 10. Canet-Aviles RM, Wilson MA, Miller DW, Ahmad R, McLendon C, et al. (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine- sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci U S A 101: 9103–9108. 11. Blackinton J, Lakshminarasimhan M, Thomas KJ, Ahmad R, Greggio E, et al. (2009) Formation of a stabilized cysteine sulfinic acid is critical for the mitochondrial function of the parkinsonism protein DJ-1. J Biol Chem. 12. Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, et al. (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5: 213–218. 13. Junn E, Jang WH, Zhao X, Jeong BS, Mouradian MM (2008) Mitochondrial localization of DJ-1 leads to enhanced neuroprotection. J Neurosci Res. 14. Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, et al. (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Biol 15: 1572–1577. 15. Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, et al. (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahy- dropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102: 5215–5220. 16. Seppet E, Gruno M, Peetsalu A, Gizatullina Z, Nguyen HP, et al. (2009) Mitochondria and energetic depression in cell pathophysiology. Int J Mol Sci 10: 2252–2303. 17. Mandemakers W, Morais VA, De Strooper B (2007) A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases. J Cell Sci 120: 1707–1716. 18. Gellerich FN, Trumbeckaite S, Muller T, Deschauer M, Chen Y, et al. (2004) Energetic depression caused by mitochondrial dysfunction. Mol Cell Biochem 256-257: 391–405. 19. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, et al. (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Embo J 27: 433–446. 20. Gorner K, Holtorf E, Waak J, Pham TT, Vogt-Weisenhorn DM, et al. (2007) Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1. J Biol Chem 282: 13680–13691. 21. Koopman WJ, Verkaart S, Visch HJ, van der Westhuizen FH, Murphy MP, et al. (2005) Inhibition of complex I of the electron transport chain causes O2-. -mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 288: C1440–1450. 22. Proikas-Cezanne T, Ruckerbauer S, Stierhof YD, Berg C, Nordheim A (2007) Human WIPI-1 puncta-formation: a novel assay to assess mammalian autophagy. FEBS Lett 581: 3396–3404. 23. Proikas-Cezanne T, Pfisterer SG (2009) Assessing mammalian autophagy by WIPI-1/Atg18 puncta formation. Methods Enzymol 452: 247–260. 24. Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, et al. (2004) WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene 23: 9314–9325. 25. Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 3: 542–545. 26. Kuznetsov AV, Veksler V, Gellerich FN, Saks V, Margreiter R, et al. (2008) Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells. Nat Protoc 3: 965–976. 27. Cerveny KL, Tamura Y, Zhang Z, Jensen RE, Sesaki H (2007) Regulation of mitochondrial fusion and division. Trends Cell Biol 17: 563–569. 28. Xue L, Fletcher GC, Tolkovsky AM (1999) Autophagy is activated by apoptotic signalling in sympathetic neurons: an alternative mechanism of death execution. Mol Cell Neurosci 14: 180–198. DJ-1 in Mitochondrial Dynamics 29. Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, et al. (2008) A block of autophagy in lysosomal storage disorders. Hum Mol Genet 17: 119–129. 30. Settembre C, Fraldi A, Rubinsztein DC, Ballabio A (2008) Lysosomal storage diseases as disorders of autophagy. Autophagy 4: 113–114. 31. Sulzer D, Mosharov E, Talloczy Z, Zucca FA, Simon JD, et al. (2008) Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease. J Neurochem 106: 24–36. 32. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451: 1069–1075. 33. Mizushima N, Ohsumi Y, Yoshimori T (2002) Autophagosome formation in mammalian cells. Cell Struct Funct 27: 421–429. 34. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, et al. (2008) Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4: 151–175. 35. Vergne I, Roberts E, Elmaoued RA, Tosch V, Delgado MA, et al. (2009) Control of autophagy initiation by phosphoinositide 3-phosphatase jumpy. Embo J 28: 2244–2258. 36. Rubinsztein DC, Cuervo AM, Ravikumar B, Sarkar S, Korolchuk V, et al. (2009) In search of an ‘‘autophagomometer’’. Autophagy 5: 585–589. 37. Farre JC, Krick R, Subramani S, Thumm M (2009) Turnover of organelles by autophagy in yeast. Curr Opin Cell Biol. 38. Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y (1991) Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 266: 17707–17712. 39. Shacka JJ, Klocke BJ, Roth KA (2006) Autophagy, bafilomycin and cell death: the ‘‘a-B-cs’’ of plecomacrolide-induced neuroprotection. Autophagy 2: 228–230. 40. Gu L, Cui T, Fan C, Zhao H, Zhao C, et al. (2009) Involvement of ERK1/2 signaling pathway in DJ-1-induced neuroprotection against oxidative stress. Biochem Biophys Res Commun 383: 469–474. 41. Dagda RK, Zhu J, Kulich SM, Chu CT (2008) Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson’s disease. Autophagy 4: 770–782. 42. Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58: 495–505. 43. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, et al. (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 100: 4078–4083. 44. Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, et al. (2007) Loss-of- function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci 27: 12413–12418. 45. Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280: 26185–26192. 46. Kuznetsov AV, Hermann M, Troppmair J, Margreiter R, Hengster P (2009) Complex Patterns of Mitochondrial Dynamics in Human Pancreatic Cells Revealed by Fluorescent Confocal Imaging. J Cell Mol Med. 47. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, et al. (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105: 1638–1643. 48. Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A 105: 14503–14508. 49. Thomas KJ, Sanderbring A, Beilina A, Van der Brug MP, Cleland M, et al. (2008) Parkinsonism associated PTEN-induced kinase 1 affects mitochondrial dynamics via phosphorylation of Dynamin-related protein 1; Washington DC. Society for Neuroscience. 50. Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, et al. (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A 103: 10793–10798. 51. Kanki T, Klionsky DJ (2008) Mitophagy in yeast occurs through a selective mechanism. J Biol Chem. 52. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462: 245–253. 53. Scherz-Shouval R, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 17: 422–427. 54. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777: 860–866. 55. Rubinsztein DC (2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443: 780–786. 56. Cataldo AM, Barnett JL, Mann DM, Nixon RA (1996) Colocalization of lysosomal hydrolase and beta-amyloid in diffuse plaques of the cerebellum and striatum in Alzheimer’s disease and Down’s syndrome. J Neuropathol Exp Neurol 55: 704–715. 57. Schapira AH (2005) Present and future drug treatment for Parkinson’s disease. J Neurol Neurosurg Psychiatry 76: 1472–1478. 58. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, et al. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301: 1387–1391. PLoS ONE | www.plosone.org 14 February 2010 | Volume 5 | Issue 2 | e9367