Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease

Stefanie Krick, Shaolin Shi, Wenjun Ju, Christian H Faul, Su Yi Tsai, Peter Mundel, Erwin P. Böttinger

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Cellular localization determines whether the serine protease HtrA2 exerts pro- or antiapoptotic functions. In contrast to the well-characterized proapoptotic function of cytosolic HtrA2, mechanisms underlying the mitochondrial protective role are poorly understood. Mpv17l is a transmembrane protein previously implicated in peroxisomal reactive oxygen species metabolism and a close homolog of the inner mitochondrial membrane protein Mpv17. Here we demonstrate a previously undescribed direct interaction between Mpv17l and HtrA2 in mitochondria. The interaction is mediated by a PDZ domain and induces protease activation of HtrA2. HtrA2 inhibits mitochondrial superoxide generation, stabilizes mitochondrial membrane potential, and prevents apoptosis at baseline and in response to extracellular inducers of mitochondrial stress. The physiological role of Mpv17l is underscored by the finding that oxidative stress-induced down-regulation of Mpv17l is a consistent feature in renal injury models. Our findings identify Mpv17l as a unique interacting protein and regulator of HtrA2 protease mediating antioxidant and antiapoptotic function in mitochondria.

Original languageEnglish
Pages (from-to)14106-14111
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number37
DOIs
StatePublished - Sep 16 2008
Externally publishedYes

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Mitochondria
Oxidative Stress
Peptide Hydrolases
Apoptosis
PDZ Domains
Mitochondrial Membrane Potential
Mitochondrial Proteins
Mitochondrial Membranes
Serine Proteases
Superoxides
Reactive Oxygen Species
Membrane Proteins
Proteins
Down-Regulation
Antioxidants
Kidney
Wounds and Injuries

Keywords

  • Hypoxia
  • Kidney injury
  • Proximal tubular epithelial cells
  • Reactive oxygen species
  • Transforming growth factor beta

ASJC Scopus subject areas

  • General

Cite this

Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease. / Krick, Stefanie; Shi, Shaolin; Ju, Wenjun; Faul, Christian H; Tsai, Su Yi; Mundel, Peter; Böttinger, Erwin P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 37, 16.09.2008, p. 14106-14111.

Research output: Contribution to journalArticle

Krick, Stefanie ; Shi, Shaolin ; Ju, Wenjun ; Faul, Christian H ; Tsai, Su Yi ; Mundel, Peter ; Böttinger, Erwin P. / Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 37. pp. 14106-14111.
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AU - Mundel, Peter

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