Abstract
Under pathophysiological conditions, aberrant mitochondrial dynamics lead to the different types of neuronal death: excessive mitochondrial fission provokes apoptosis and abnormal mitochondrial elongation induces necrosis. However, the underlying mechanisms how the different mitochondrial dynamics result in the distinct neuronal death patterns have been elusive. In the present study, status epilepticus (SE) evoked excessive mitochondrial fission in parvalbumin (PV) cells (one of GABAergic interneurons) and abnormal mitochondrial elongation in CA1 neurons in the rat hippocampus. These impaired mitochondrial dynamics were accompanied by mitochondrial translocations of active caspase-3 and high mobility group box 1 (HMGB1) in PV cells and CA1 neurons, respectively. WY14643 (an activator of mitochondrial fission) aggravated SE-induced PV cell loss by enhancing active caspase-3 induction and its mitochondrial translocation, which were attenuated by Mdivi-1 (an inhibitor of mitochondrial fission). Mitochondrial HMGB1 import was not observed in PV cell. In contrast to PV cells, Mdivi-1 deteriorated SE-induced CA1 neuronal death concomitant with mitochondrial HMGB1 translocation, which was abrogated by WY14643. These findings suggest that SE-induced aberrant mitochondrial dynamics may be involved in translocation of active caspase-3 and HMGB1 into mitochondria, which regulate neuronal apoptosis and necrosis, respectively.
Highlights
Mitochondria play an essential role in bioenergetics and respiratory functions for cell viability
Since status epilepticus (SE) leads to PV cell apoptosis via excessive mitochondrial fission (Kim and Kang, 2017), we first investigated the relevance between mitochondrial dynamics and mitochondrial active caspase-3 transports
We have reported that excessive mitochondrial fissions lead to apoptosis of PV cells in dentate gyrus following SE (Kim and Kang, 2017), while aberrant mitochondrial elongations evokes programed necrosis of CA1 neurons and dentate granule cells (Kim et al, 2014; Hyun et al, 2016; Ko and Kang, 2017)
Summary
Mitochondria play an essential role in bioenergetics and respiratory functions for cell viability. Imbalance of mitochondrial dynamics lead to the distinct neuronal death under stressful conditions (Youle and Karbowski, 2005; Parone et al, 2008; DuBoff et al, 2012; Kim et al, 2014; Kim and Kang, 2017): Excessive mitochondrial fission provokes the impaired mitochondrial function triggering apoptosis. SE provokes aberrant mitochondrial elongation in CA1 neurons (Kim et al, 2014; Hyun et al, 2016), but it propels excessive mitochondrial fragmentation in PV cell (Kim and Kang, 2017). The underlying mechanisms how the different mitochondrial dynamics lead to the distinct neuronal death patterns have been elusive
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