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PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for the local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for the activation of mitophagy.
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http://dx.doi.org/10.1016/j.neuron.2022.01.035 | DOI Listing |
Behav Brain Res
September 2025
Department of neurology, Hebei Medical University Third Hospital, Hebei 050000,Shijiazhuang,China; Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Hebei 050000,Shijiazhuang,China. Electronic address:
Background: Mitochondrial dysfunction is considered to be an important pathogenesis of cognitive impairment in Alzheimer's disease(AD). Activation of Nrf2 can improve cognitive impairment in AD mice, but the underlying mechanism remains to be elucidated. This research aims to investigate the intrinsic molecular mechanism of Nrf2 in mitochondrial biogenesis related to cognitive impairment of AD mice.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
September 2025
Department of Physiology and Pathophysiology, University of Manitoba, Health Sciences Centre, Winnipeg, Canada. Electronic address:
Ferroptosis is a recently discovered lytic form of cell death that is triggered by iron-driven excessive lipid peroxidation and depletion of glutathione and glutathione peroxidase-4 (GPX4). This form of cell death has been linked to a wide range of conditions from cancer to neurodegenerative diseases. Using murine hippocampal HT22 neurons, we aimed to investigate the underlying mechanisms of glutamate-mediated ferroptosis.
View Article and Find Full Text PDFFree Radic Biol Med
September 2025
Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, The First Affiliated Hospital of Guangxi Medical University,Nanning, Guangxi 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education,
Background: The second most common cause of autosomal recessive early-onset Parkinson's disease (PD) can be attributed to mutations in the PINK1 gene, malfunction of the mitochondria is the key pathological mechanism. Bre1 encodes an E3 ubiquitin ligase, with the discovery of Bre1's role in repairing mitochondrial damage, further investigation into its implications for PD is warranted.
Methods: We used the PINK1B9 drosophila melanogaster as the PD model.
Psychiatry Res
September 2025
Department of Nautical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, PR China. Electronic address:
Aims: Running exercise has demonstrated efficacy in the prevention and treatment of depression, yet the underlying mechanisms remain incompletely elucidated. Mitochondrial dysfunction and impaired mitophagy have been implicated in depression pathogenesis, while SIRT1 has been shown to play a critical role in both depression and mitochondrial regulation. Building on these established associations, this study aimed to investigate the antidepressant mechanisms of running exercise, with particular fucus on mitophagy regulated by SIRT1.
View Article and Find Full Text PDFThe brain is a metabolically demanding organ as it orchestrates and stabilizes neuronal network activity through plasticity. This mechanism imposes enormous and prolonged energetic demands at synapses, yet it is unclear how these needs are met in a sustained manner. Mitochondria serve as a local energy supply for dendritic spines, providing instant and sustained energy during synaptic plasticity.
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