Abstract

We have been working on the mitochondrial kinase PINK1, with a particular focus on how loss of function of PINK1 influences mitochondria. Extending previous work, we have shown that absence of PINK1 leads to a number of mitochondrial abnormalities including some evidence of fragmentation, at least in cells in culture. Working on the signaling pathways involved, we have found that cells lacking PINK1 are more sensitive to C2-ceramide, which likely signals through the Akt pathway. Related to this, we have also found that Akt-mediated changes in hexokinase, a mitochondrial protein, control the recruitment of parkin to mitochondria. We plan to further develop this project by examining the role(s) of hexokinase in maintenance of mitochondrial function in the brain.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000940-07
Application #
8931627
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Soutar, Marc P M; Kempthorne, Liam; Miyakawa, Shuichi et al. (2018) AKT signalling selectively regulates PINK1 mitophagy in SHSY5Y cells and human iPSC-derived neurons. Sci Rep 8:8855
Parrado-Fernández, Cristina; Schneider, Bernadette; Ankarcrona, Maria et al. (2018) Reduction of PINK1 or DJ-1 impair mitochondrial motility in neurites and alter ER-mitochondria contacts. J Cell Mol Med :
Hauser, David N; Primiani, Christopher T; Cookson, Mark R (2017) The Effects of Variants in the Parkin, PINK1, and DJ-1 Genes along with Evidence for their Pathogenicity. Curr Protein Pept Sci 18:702-714
Hauser, David N; Primiani, Christopher T; Langston, Rebekah G et al. (2015) The Polg Mutator Phenotype Does Not Cause Dopaminergic Neurodegeneration in DJ-1-Deficient Mice. eNeuro 2:
Rojas-Charry, Liliana; Cookson, Mark R; Niño, Andrea et al. (2014) Downregulation of Pink1 influences mitochondrial fusion-fission machinery and sensitizes to neurotoxins in dopaminergic cells. Neurotoxicology 44:140-8
Hauser, David N; Dillman, Allissa A; Ding, Jinhui et al. (2014) Post-translational decrease in respiratory chain proteins in the Polg mutator mouse brain. PLoS One 9:e94646
McCoy, Melissa K; Kaganovich, Alice; Rudenko, Iakov N et al. (2013) Hexokinase activity is required for recruitment of parkin to depolarized mitochondria. Hum Mol Genet :
McCoy, Melissa K; Cookson, Mark R (2012) Mitochondrial quality control and dynamics in Parkinson's disease. Antioxid Redox Signal 16:869-82
McCoy, Melissa K; Cookson, Mark R (2011) DJ-1 regulation of mitochondrial function and autophagy through oxidative stress. Autophagy 7:531-2
Thomas, Kelly Jean; McCoy, Melissa K; Blackinton, Jeff et al. (2011) DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet 20:40-50

Showing the most recent 10 out of 15 publications