Loss of HtrA2/Omi activity in non-neuronal tissues of adult mice causes premature aging

    Authors

    S. Kang; J. P. Louboutin; P. Datta; C. P. Landel; D. Martinez; A. S. Zervos; D. S. Strayer; T. Fernandes-Alnemri;E. S. Alnemri

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    Abbreviated Journal Title

    Cell Death Differ.

    Keywords

    HtrA2; mitochondria; quality control; aging; neurodegeneration; mitochondrial DNA; MITOCHONDRIAL-DNA MUTATIONS; SPASTIC PARAPLEGIA; OXIDATIVE STRESS; QUALITY-CONTROL; CELL-DEATH; PROTEASE; OPA1; AUTOPHAGY; FUSION; MUSCLE; Biochemistry & Molecular Biology; Cell Biology

    Abstract

    mnd2 mice die prematurely as a result of neurodegeneration 30-40 days after birth due to loss of the enzymatic activity of the mitochondrial quality control protease HtrA2/Omi. Here, we show that transgenic expression of human HtrA2/Omi in the central nervous system of mnd2 mice rescues them from neurodegeneration and prevents their premature death. Interestingly, adult transgenic mnd2 mice develop accelerated aging phenotypes, such as premature weight loss, hair loss, reduced fertility, curvature of the spine, heart enlargement, increased autophagy, and death by 12-17 months of age. These mice also have elevated levels of clonally expanded mitochondrial DNA (mtDNA) deletions in their tissues. Our results provide direct genetic evidence linking mitochondrial protein quality control to mtDNA deletions and aging in mammals. Cell Death and Differentiation (2013) 20,259-269; doi:10.1038/cdd.2012.117; published online 14 September 2012

    Journal Title

    Cell Death and Differentiation

    Volume

    20

    Issue/Number

    2

    Publication Date

    1-1-2013

    Document Type

    Article

    Language

    English

    First Page

    259

    Last Page

    269

    WOS Identifier

    WOS:000314141800009

    ISSN

    1350-9047

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