A5038773672- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Web Data Mining and Analysis
- Genetic Neurodegenerative Diseases
- Context-Aware Activity Recognition Systems
- EEG and Brain-Computer Interfaces
- Complex Network Analysis Techniques
- Plant Reproductive Biology
- Indoor and Outdoor Localization Technologies
- Innovative Teaching and Learning Methods
- Lysosomal Storage Disorders Research
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Amyotrophic Lateral Sclerosis Research
- Gaze Tracking and Assistive Technology
- Natural Language Processing Techniques
- Robotics and Automated Systems
- Recommender Systems and Techniques
- Photosynthetic Processes and Mechanisms
- Hand Gesture Recognition Systems
- Neurological diseases and metabolism
University of Toyama
2019-2024
Tokyo Metropolitan Institute of Medical Science
2015-2024
Tokyo Medical and Dental University
2022-2024
Wakayama University
2010-2019
Japan Science and Technology Agency
2015-2016
Universitas Muhammadiyah Metro
2016
Judd Systems Technologies (United States)
2015
University of Tsukuba
1995-2014
Juntendo University
2013
Nippon Soken (Japan)
2006
Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Recent identification of genes linked to familial forms PD such as Parkin and PINK1 (PTEN-induced putative kinase 1) has revealed that ubiquitylation mitochondrial integrity are key factors in pathogenesis. However, the exact mechanism underlying functional interplay between Parkin-catalyzed PINK1-regulated quality control remains an enigma. In this study, we show rapidly constitutively degraded under steady-state conditions...
Dysfunction of PINK1, a mitochondrial Ser/Thr kinase, causes familial Parkinson's disease (PD). Recent studies have revealed that PINK1 is rapidly degraded in healthy mitochondria but accumulates on the membrane potential (ΔΨm)-deficient mitochondria, where it recruits another PD gene product, Parkin, to ubiquitylate damaged mitochondria. Despite extensive study, mechanism underlying homeostatic control remains unknown. Here we report autophosphorylated following decrease ΔΨm and most...
PINK1 and Parkin were first identified as the causal genes responsible for familial forms of early-onset Parkinson's disease (PD), a prevalent neurodegenerative disorder. encodes mitochondrial serine/threonine protein kinase, whereas an ubiquitin-protein ligase. cooperate to maintain integrity; however, detailed molecular mechanism how Parkin-catalyzed ubiquitylation results in integrity remains enigma. In this study, we show that K63-linked polyubiquitylation depolarized mitochondria...
PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and removal of damaged via ubiquitylation. Dysfunction this process predisposes development familial recessive Parkinson’s disease. Although various models the recruitment have been proposed, none them adequately explain accumulated data, thus molecular basis remains be fully elucidated. In study, we show that a linear ubiquitin chain phosphomimetic tetra-ubiquitin(S65D) energized in absence PINK1, whereas wild-type...
Damaged mitochondria are selectively eliminated in a process called mitophagy. Parkin and PINK1, proteins mutated Parkinson's disease, amplify ubiquitin signals on damaged with the subsequent activation of autophagic machinery. Autophagy adaptors thought to link ubiquitinated autophagy through ATG8 protein binding. Here, we establish methods for inducing mitophagy by mitochondria-targeted chains chemical-induced mitochondrial ubiquitination. Using these tools, reveal that signal is...
Abstract Tank-binding kinase 1 (TBK1) is a Ser/Thr that involved in many intracellular processes, such as innate immunity, cell cycle, and apoptosis. TBK1 also important for phosphorylating the autophagy adaptors mediate selective autophagic removal of damaged mitochondria. However, mechanism by which PINK1-Parkin-mediated mitophagy activates remains largely unknown. Here, we show adaptor optineurin (OPTN) provides unique platform activation. Both OPTN-ubiquitin OPTN-pre-autophagosomal...
Mitochondrial and lysosomal functions are intimately linked critical for cellular homeostasis, as evidenced by the fact that senescence, aging, multiple prominent diseases associated with concomitant dysfunction of both organelles. However, it is not well understood how two important organelles regulated. Transcription factor EB (TFEB) master regulator function also implicated in regulating mitochondrial function; however, mechanism underlying maintenance remains to be fully elucidated....
PINK1 and PARKIN are causal genes for autosomal recessive familial Parkinsonism. is a mitochondrial Ser/Thr kinase, whereas Parkin functions as an E3 ubiquitin ligase. Under steady-state conditions, localizes to the cytoplasm where its activity repressed. A decrease in membrane potential triggers recruits it depolarized mitochondria ubiquitylation of substrates. The molecular basis how re-established by damage has yet be determined. Here we provide vitro biochemical evidence...
Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson's disease, play essential roles mitophagy through ubiquitination of mitochondria. Cargo E3 ubiquitin ligase is important to trigger selective autophagy. Although autophagy receptors recruit LC3-labeled autophagic membranes onto damaged mitochondria, how other units such as ATG9A-integrated vesicles recruited remains unclear. Here, using mammalian cultured cells, we...
Dysfunction of PTEN-induced putative kinase 1 (PINK1), a Ser/Thr with an N-terminal mitochondria targeting sequence (MTS), causes familial recessive Parkinsonism. Reduction the mitochondrial membrane potential limits MTS-mediated matrix import and promotes PINK1 accumulation on outer (OMM) depolarized mitochondria. then undergoes autophosphorylation phosphorylates ubiquitin Parkin, cytosolic ligase, for clearance damaged The molecular basis localization OMM rather than release to cytosol is...
Significance Although lysosomes play a crucial role in autophagy, damaged are eliminated by autophagy. The molecular mechanisms that recognize lysosomal damage cells remain poorly understood, but ubiquitination is known prerequisite for directing autophagic machinery to lysosomes. FBXO27, substrate-recognition subunit of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, localizes cytosolic surface endomembranes and binds glycoproteins. This paper reports FBXO27 ubiquitinates...
PINK1 is activated by autophosphorylation and forms a high-molecular-weight complex, thereby initiating the selective removal of damaged mitochondria autophagy. Other than translocase outer mitochondrial membrane complexes, members PINK1-containing protein complexes remain obscure. By mass spectrometric analysis co-immunoprecipitates, we identify inner TIM23 as component complex. downregulation decreases levels significantly delays autophosphorylation, indicating that promotes accumulation...
Summary EL5 , a rice gene responsive to N ‐acetylchitooligosaccharide elicitor, encodes RING‐H2 finger protein with structural features common the plant‐specific ATL family. We show that fusion of maltose binding (MBP) was polyubiquitinated by incubation ubiquitin, ubiquitin‐activating enzyme (E1), and Ubc4/5 subfamily ubiquitin‐conjugating (E2). possesses activity catalyse transfer ubiquitin MBP moiety, motif is necessary for this activity. Thus, we concluded represents ligase (E3). also...