| First Author | Goo HG | Year | 2014 |
| Journal | Exp Cell Res | Volume | 328 |
| Issue | 2 | Pages | 456-65 |
| PubMed ID | 25094062 | Mgi Jnum | J:217559 |
| Mgi Id | MGI:5614535 | Doi | 10.1016/j.yexcr.2014.07.032 |
| Citation | Goo HG, et al. (2014) HtrA2/Omi influences the stability of LON protease 1 and prohibitin, proteins involved in mitochondrial homeostasis. Exp Cell Res 328(2):456-65 |
| abstractText | 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. |
