HtrA2/Omi influences the stability of LON protease 1 and prohibitin, proteins involved in mitochondrial homeostasis

Hui Gwan Goo, Hyangshuk Rhim, Seongman Kang

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


High temperature requirement A2 (HtrA2)/Omi is a serine protease localized in mitochondria. In response to apoptotic stimuli, HtrA2 is released to the cytoplasm and cleaves many proteins, including XIAP, Apollon/BRUCE, WT1, and Ped/Pea-15, to promote apoptosis. However, the function of HtrA2 in mitochondria under normal conditions remains unclear. Here, we show that the mitochondrial proteins, LON protease 1 (LONP1) and prohibitin (PHB), are overexpressed in HtrA2-/- mouse embryonic fibroblast (MEF) cells and HtrA2 knock-down HEK293T cells. We also confirm the effect of the HtrA2 protease on the stability of the above mitochondrial quality control proteins in motor neuron degeneration 2 (mnd2) mice, which have a greatly reduced protease activity as a result of a Ser276Cys missense mutation of the HtrA2 gene. In addition, PHB interacts with and is directly cleaved by HtrA2. Luminescence assays demonstrate that the intracellular ATP level is decreased in HtrA2-/- cells compared to HtrA2+/+ cells. HtrA2 deficiency causes a decrease in the mitochondrial membrane potential, and reactive oxygen species (ROS) generation is greater in HtrA2-/- cells than in HtrA2+/+ cells. Our results implicate that HtrA2 might be an upstream regulator of mitochondrial homeostasis.

Original languageEnglish
Pages (from-to)456-465
Number of pages10
JournalExperimental Cell Research
Issue number2
Publication statusPublished - 2014 Nov 1

Bibliographical note

Funding Information:
We are grateful to Dr. Julian Downward at Cancer Research UK London Research Institute for offering HtrA2 +/+ and HtrA2 −/− MEF cells. This study was supported by a Grant from the National R&D Program for Cancer Control, the Ministry of Health & Welfare, Republic of Korea ( 1320010 ) and by a Korea University Grant.

Publisher Copyright:
© 2014 Elsevier Inc.


  • HtrA2
  • Mitochondria
  • Mitochondrial homeostasis
  • Mnd2
  • PHB
  • Protein quality control

ASJC Scopus subject areas

  • Cell Biology


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