Furthermore, PAB induced phosphorylation of DRP1 at Ser616 and mitochondrial fission. It disrupted mitochondrial membrane potential (MMP) and impaired ATP production. PAB inhibited the viability of and induced apoptosis in Hepa1-6 cells in a dose-dependent manner. In the present study, we investigated the mechanism through which PAB exert its anticancer effects in hepatocellular carcinoma (HCC). However, the underlying mechanisms remain largely unclear. Pseudolaric acid B (PAB), a natural product isolated from the root bark of Pseudolarix kaempferi, has been reported to exert inhibitory effects in various cancers. MitoTimer reporter assay can specifically target to mitochondria and be used to monitor mitochondrial biogenesis and maturation as well as turnover in vitro and in vivo. Super-resolution microscopy analysis revealed that majority of mitochondria were spatially heterogeneous with proteins from simultaneous new synthesis, maturation, and turnover in hepatocytes. The ratio of red/green fluorescence in each cell will be used to track mitochondrial aging. Three types of mitochondria were visualized in mouse hepatocytes: green-only mitochondria (newly synthesized mitochondria), red-only mitochondria (old/aging mitochondria), as well as the majority of yellow mitochondria (representing an intermediate stage of mitochondria). We describe a detailed protocol for monitoring mitochondrial lifecycle in primary cultured mouse hepatocytes and mouse liver using the dual color fluorescence-based imaging of MitoTimer. Altered mitochondrial biogenesis and mitophagy are closely related to many chronic diseases, highlighting the importance of mitochondrial stasis in various pathological conditions including liver diseases. Mitochondrial biogenesis and turnover rate are critical to maintain homeostasis of the intracellular mitochondrial pool. Herein we review the available evidence regarding the regulation of mitochondrial dynamics by neuronal activity and by neuromodulators, and how these changes in the activity of mitochondria affect synaptic communication. Therefore, mitochondria activity at the synapse allows the integration of different signals and the organelles are important players in the response to synaptic stimulation. These signals act by controlling the distribution of mitochondria and by regulating their activity. The transport of mitochondria along neurites is a highly regulated process, being modulated by the pattern of neuronal activity and by extracellular cues that interact with surface receptors. Biogenesis of synaptic mitochondria takes place in the cell body, and these organelles are then transported to the synapse by motor proteins that carry their cargo along microtubule tracks. Mitochondria are present in the pre- and post-synaptic regions, providing the energy required for the activity of these very specialized neuronal compartments.
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