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

Hui Gwan Goo, Hyangshuk Rhim, Seong Man Kang

Research output: Contribution to journalArticle

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Abstract

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
Volume328
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

varespladib methyl
Homeostasis
Peptide Hydrolases
Temperature
Proteins
prohibitin
Mitochondria
X-Linked Inhibitor of Apoptosis Protein
Nerve Degeneration
Mitochondrial Membrane Potential
Mitochondrial Proteins
Peas
Serine Proteases
Motor Neurons
Missense Mutation
Luminescence
Quality Control
Reactive Oxygen Species
Cytoplasm
Fibroblasts

ASJC Scopus subject areas

  • Cell Biology

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HtrA2/Omi influences the stability of LON protease 1 and prohibitin, proteins involved in mitochondrial homeostasis. / Goo, Hui Gwan; Rhim, Hyangshuk; Kang, Seong Man.

In: Experimental Cell Research, Vol. 328, No. 2, 01.01.2014, p. 456-465.

Research output: Contribution to journalArticle

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