University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medical Biology
  • Medical Biology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.

    Thumbnail
    Download
    Published version (2.933Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    45
    42
    Author
    Schüll, S; Günther, SD; Brodesser, S; Seeger, JM; Tosetti, B; Wiegmann, K; Pongratz, C; Diaz, F; Witt, A; Andree, M; ...
    Date
    2015-03-12
    Source Title
    Cell Death and Disease
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Brinkmann, Kerstin
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Schüll, S., Günther, S. D., Brodesser, S., Seeger, J. M., Tosetti, B., Wiegmann, K., Pongratz, C., Diaz, F., Witt, A., Andree, M., Brinkmann, K., Krönke, M., Wiesner, R. J. & Kashkar, H. (2015). Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.. Cell Death Dis, 6 (3), pp.e1691-. https://doi.org/10.1038/cddis.2015.62.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256224
    DOI
    10.1038/cddis.2015.62
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385940
    Abstract
    Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the specific alteration of the cytochrome c oxidase (COX), representing a common defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in response to oxidative stress. Our data identified an increased ceramide synthase 6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction induced either by chemical or genetic approaches. The elevated CerS6 activity resulted in accumulation of the pro-apoptotic C16 : 0 ceramide, which facilitates the mitochondrial apoptosis in response to oxidative stress. Accordingly, inhibition of CerS6 or its specific knockdown diminished the increased susceptibility of COX-deficient cells to oxidative stress. Our results provide new insights into how mitochondrial RC dysfunction mechanistically interferes with the apoptotic machinery. On the basis of its pivotal role in regulating cell death upon COX dysfunction, CerS6 might potentially represent a novel target for therapeutic intervention in mitochondrial diseases caused by COX dysfunction.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Medical Biology - Research Publications [865]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors