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- Title
LONP1 Regulates Mitochondrial Accumulations of HMGB1 and Caspase-3 in CA1 and PV Neurons Following Status Epilepticus.
- Authors
Kim, Ji-Eun; Park, Hana; Kim, Tae-Hyun; Kang, Tae-Cheon; Côrte-Real, Manuela
- Abstract
Lon protease 1 (LONP1) is a highly conserved serine peptidase that plays an important role in the protein quality control system in mammalian mitochondria. LONP1 catalyzes the degradation of oxidized, dysfunctional, and misfolded matrix proteins inside mitochondria and regulates mitochondrial gene expression and genome integrity. Therefore, LONP1 is up-regulated and suppresses cell death in response to oxidative stress, heat shock, and nutrient starvation. On the other hand, translocation of high mobility group box 1 (HMGB1) and active caspase-3 into mitochondria is involved in apoptosis of parvalbumin (PV) cells (one of the GABAergic interneurons) and necrosis of CA1 neurons in the rat hippocampus, respectively, following status epilepticus (SE). In the present study, we investigated whether LONP1 may improve neuronal viability to prevent or ameliorate translocation of active caspase-3 and HMGB1 in mitochondria within PV and CA1 neurons. Following SE, LONP1 expression was up-regulated in mitochondria of PV and CA1 neurons. LONP1 knockdown deteriorated SE-induced neuronal death with mitochondrial accumulation of active caspase-3 and HMGB1 in PV cells and CA1 neurons, respectively. LONP1 knockdown did not affect the aberrant mitochondrial machinery induced by SE. Therefore, our findings suggest, for the first time, that LONP1 may contribute to the alleviation of mitochondrial overloads of active caspase-3 and HMGB1, and the maintenance of neuronal viability against SE.
- Subjects
STATUS epilepticus; NEURONS; MITOCHONDRIA; SOLAR cells; EXTRACELLULAR matrix proteins; INTERNEURONS; PLANT mitochondria
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 5, p2275
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22052275