Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases

P. Hemachandra Reddy, Tejaswini P. Reddy, Maria Manczak, Marcus J. Calkins, Ulziibat Shirendeb, Peizhong Mao

    Research output: Contribution to journalReview article

    168 Scopus citations

    Abstract

    The purpose of this article is to review the recent developments of abnormal mitochondrial dynamics, mitochondrial fragmentation, and neuronal damage in neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The GTPase family of proteins, including fission proteins, dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1), and fusion proteins (Mfn1, Mfn2 and Opa1) are essential to maintain mitochondrial fission and fusion balance, and to provide necessary adenosine triphosphate to neurons. Among these, Drp1 is involved in several important aspects of mitochondria, including shape, size, distribution, remodeling, and maintenance of mitochondria in mammalian cells. In addition, recent advancements in molecular, cellular, electron microscopy, and confocal imaging studies revealed that Drp1 is associated with several cellular functions, including mitochondrial and peroxisomal fragmentation, phosphorylation, SUMOylation, ubiquitination, and cell death. In the last two decades, tremendous progress has been made in researching mitochondrial dynamics, in yeast, worms, and mammalian cells; and this research has provided evidence linking Drp1 to neurodegenerative diseases. Researchers in the neurodegenerative disease field are beginning to recognize the possible involvement of Drp1 in causing mitochondrial fragmentation and abnormal mitochondrial dynamics in neurodegenerative diseases. This article summarizes research findings relating Drp1 to mitochondrial fission and fusion, in yeast, worms, and mammals. Based on findings from the Reddy laboratory and others', we propose that mutant proteins of neurodegenerative diseases, including AD, PD, HD, and ALS, interact with Drp1, activate mitochondrial fission machinery, fragment mitochondria excessively, and impair mitochondrial transport and mitochondrial dynamics, ultimately causing mitochondrial dysfunction and neuronal damage.

    Original languageEnglish (US)
    Pages (from-to)103-118
    Number of pages16
    JournalBrain Research Reviews
    Volume67
    Issue number1-2
    DOIs
    StatePublished - Jun 24 2011

    Keywords

    • Abnormal mitochondrial dynamics
    • Alzheimer's disease
    • Dynamin related protein 1
    • Mitochondrial fission

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Clinical Neurology

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  • Cite this

    Reddy, P. H., Reddy, T. P., Manczak, M., Calkins, M. J., Shirendeb, U., & Mao, P. (2011). Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Research Reviews, 67(1-2), 103-118. https://doi.org/10.1016/j.brainresrev.2010.11.004