Search

Your search keyword '"Sesaki, Hiromi"' showing total 612 results
Start Over Author "Sesaki, Hiromi"
612 results on '"Sesaki, Hiromi"'

7. Longitudinal tracking of neuronal mitochondria delineates PINK1/Parkin-dependent mechanisms of mitochondrial recycling and degradation

Author

Li, Huihui, Doric, Zak, Berthet, Amandine, Jorgens, Danielle M, Nguyen, Mai K, Hsieh, Ivy, Margulis, Julia, Fang, Rebecca, Debnath, Jayanta, Sesaki, Hiromi, Finkbeiner, Steve, Huang, Eric, and Nakamura, Ken

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurosciences, Neurodegenerative, Parkinson's Disease, Brain Disorders, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Neurological
Abstract

Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons. We combined time-lapse microscopy and correlative light and electron microscopy to track individual mitochondria in neurons lacking the fission-promoting protein dynamin-related protein 1 (Drp1) and delineate the kinetics of PINK1-dependent pathways of mitochondrial quality control. Depolarized mitochondria recruit Parkin to the outer mitochondrial membrane, triggering autophagosome formation, rapid lysosomal fusion, and Parkin redistribution. Unexpectedly, these mitolysosomes are dynamic and persist for hours. Some are engulfed by healthy mitochondria, and others are deacidified before bursting. In other cases, Parkin is directly recruited to the matrix of polarized mitochondria. Loss of PINK1 blocks Parkin recruitment, causes LC3 accumulation within mitochondria, and exacerbates Drp1KO toxicity to dopamine neurons. These results define a distinct neuronal mitochondrial life cycle, revealing potential mechanisms of mitochondrial recycling and signaling relevant to neurodegeneration.

Published
2021

11. Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Author

Li, Xin, Yang, Li, Mao, Zhengmei, Pan, Xueyang, Zhao, Yueshui, Gu, Xue, Eckel‐Mahan, Kristin, Zuo, Zhongyuan, Tong, Qiang, Hartig, Sean M, Cheng, Xiaodong, Du, Guangwei, Moore, David D, Bellen, Hugo J, Sesaki, Hiromi, and Sun, Kai

Subjects
Biochemistry and Cell Biology, Biological Sciences, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, 3T3 Cells, Adipocytes, Adipose Tissue, Animals, Autophagy, Cell Line, Dynamins, Endoplasmic Reticulum, HEK293 Cells, Humans, Lipid Droplets, Lipid Metabolism, Male, Mice, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, ER retention, LD budding, LD morphology, energy expenditure, lipolysis, Physiology, Medical Physiology, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical physiology
Abstract

Dynamin-Related-Protein 1 (DRP1) critically regulates mitochondrial and peroxisomal fission in multicellular organisms. However, the impact of DRP1 on other organelles, especially its direct influence on ER functions remains largely unclear. Here, we report that DRP1 translocates to endoplasmic reticulum (ER) in response to β-adrenergic stimulation. To further investigate the function of DRP1 on ER-lipid droplet (LD) dynamics and the metabolic subsequences, we generated an adipose tissue-specific DRP1 knockout model (Adipo-Drp1flx/flx ). We found that the LDs in adipose tissues of Adipo-Drp1flx/flx mice exhibited more unilocular morphology with larger sizes, and formed less multilocular structures upon cold exposure. Mechanistically, we discovered that abnormal LD morphology occurs because newly generated micro-LDs fail to dissociate from the ER due to DRP1 ablation. Conversely, the ER retention of LDs can be rescued by the overexpressed DRP1 in the adipocytes. The alteration of LD dynamics, combined with abnormal mitochondrial and autophagy functions in adipose tissue, ultimately lead to abnormalities in lipid metabolism in Adipo-Drp1flx/flx mice.

Published
2020

12. Endoplasmic reticulum–associated degradation regulates mitochondrial dynamics in brown adipocytes

Author

Zhou, Zhangsen, Torres, Mauricio, Sha, Haibo, Halbrook, Christopher J, Van den Bergh, Françoise, Reinert, Rachel B, Yamada, Tatsuya, Wang, Siwen, Luo, Yingying, Hunter, Allen H, Wang, Chunqing, Sanderson, Thomas H, Liu, Meilian, Taylor, Aaron, Sesaki, Hiromi, Lyssiotis, Costas A, Wu, Jun, Kersten, Sander, Beard, Daniel A, and Qi, Ling

Subjects
Biochemistry and Cell Biology, Biological Sciences, Adipocytes, Brown, Animals, Cold Temperature, Endoplasmic Reticulum Stress, Endoplasmic Reticulum-Associated Degradation, Intracellular Signaling Peptides and Proteins, Mice, Mice, Mutant Strains, Mitochondria, Mitochondrial Dynamics, Mitochondrial Membranes, Receptors, sigma, Thermogenesis, Ubiquitin-Protein Ligases, General Science & Technology
Abstract

The endoplasmic reticulum (ER) engages mitochondria at specialized ER domains known as mitochondria-associated membranes (MAMs). Here, we used three-dimensional high-resolution imaging to investigate the formation of pleomorphic "megamitochondria" with altered MAMs in brown adipocytes lacking the Sel1L-Hrd1 protein complex of ER-associated protein degradation (ERAD). Mice with ERAD deficiency in brown adipocytes were cold sensitive and exhibited mitochondrial dysfunction. ERAD deficiency affected ER-mitochondria contacts and mitochondrial dynamics, at least in part, by regulating the turnover of the MAM protein, sigma receptor 1 (SigmaR1). Thus, our study provides molecular insights into ER-mitochondrial cross-talk and expands our understanding of the physiological importance of Sel1L-Hrd1 ERAD.

Published
2020

13. An LKB1–mitochondria axis controls TH17 effector function

Author

Baixauli, Francesc, Piletic, Klara, Puleston, Daniel J., Villa, Matteo, Field, Cameron S., Flachsmann, Lea J., Quintana, Andrea, Rana, Nisha, Edwards-Hicks, Joy, Matsushita, Mai, Stanczak, Michal A., Grzes, Katarzyna M., Kabat, Agnieszka M., Fabri, Mario, Caputa, George, Kelly, Beth, Corrado, Mauro, Musa, Yaarub, Duda, Katarzyna J., Mittler, Gerhard, O’Sullivan, David, Sesaki, Hiromi, Jenuwein, Thomas, Buescher, Joerg M., Pearce, Edward J., Sanin, David E., and Pearce, Erika L.

Published
2022
Full Text
View/download PDF

23. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

Author

Zhang, Liang, Trushin, Sergey, Christensen, Trace A, Bachmeier, Benjamin V, Gateno, Benjamin, Schroeder, Andreas, Yao, Jia, Itoh, Kie, Sesaki, Hiromi, Poon, Wayne W, Gylys, Karen H, Patterson, Emily R, Parisi, Joseph E, Diaz Brinton, Roberta, Salisbury, Jeffrey L, and Trushina, Eugenia

Subjects
Brain, Mitochondria, Animals, Mice, Transgenic, Mice, Knockout, Alzheimer Disease, Disease Models, Animal, Dynamins, Amyloid beta-Protein Precursor, Energy Metabolism, Phosphorylation, Phenotype, CA1 Region, Hippocampal, Mitochondrial Dynamics, Hypoxia, Mice, Transgenic, Knockout, Disease Models, Animal, CA1 Region, Hippocampal
Abstract

Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

Published
2016

25. Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons

Author

Berthet, Amandine, Margolis, Elyssa B, Zhang, Jue, Hsieh, Ivy, Zhang, Jiasheng, Hnasko, Thomas S, Ahmad, Jawad, Edwards, Robert H, Sesaki, Hiromi, Huang, Eric J, and Nakamura, Ken

Subjects
Brain Disorders, Neurosciences, Parkinson's Disease, Neurodegenerative, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Animals, Axons, Dopaminergic Neurons, Dynamins, Female, Male, Membrane Potentials, Mesencephalon, Mice, Mice, Knockout, Mitochondria, Mitochondrial Dynamics, Organ Culture Techniques, axon, Drp1, mitochondria, neurodegeneration, Parkinson's disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons.

Published
2014

29. Mitochondrial Fission Mediates Endothelial Inflammation

Author

Forrester, Steven J., Preston, Kyle J., Cooper, Hannah A., Boyer, Michael J., Escoto, Kathleen M., Poltronetti, Anthony J., Elliott, Katherine J., Kuroda, Ryohei, Miyao, Masashi, Sesaki, Hiromi, Akiyama, Tomoko, Kimura, Yayoi, Rizzo, Victor, Scalia, Rosario, and Eguchi, Satoru

Published
2020
Full Text
View/download PDF

30. Mitochondrial dynamics in neurodegeneration

Author

Itoh, Kie, Nakamura, Ken, Iijima, Miho, and Sesaki, Hiromi

Subjects
Biochemistry and Cell Biology, Biological Sciences, Neurodegenerative, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Generic health relevance, Alzheimer Disease, Animals, Biological Transport, Cell Death, Dynamins, GTP Phosphohydrolases, Humans, Mammals, Microtubule-Associated Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, Mitophagy, Mutation, Neurodegenerative Diseases, Optic Atrophy, Autosomal Dominant, Oxidative Stress, mitochondria, fission, fusion, dynamin-related GTPase, neurodegeneration, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

It has been only 15 years since studies began on the molecular mechanisms underlying mitochondrial fission and fusion using simple model organisms such as Drosophila, yeast, and Caenorhabditis elegans. Beyond the primary functions of mitochondrial fission and fusion in controlling organelle shape, size, and number, it became clear that these dynamic processes are also critical to regulating cell death, mitophagy, and organelle distribution. Now, studies suggest that prominent changes occur in mitochondrial dynamics in a broad array of neurodegenerative diseases, and there is substantial evidence suggesting a key role in disease pathogenesis because neurons are among the most energy-consuming cell types and have a highly developed cell shape. Here, we review the recent findings on mitochondrial dynamics in neurodegeneration.

Published
2013

38. Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation

Author

Ma, Xiaowen, Chen, Allen, Melo, Luma, Clemente-Sanchez, Ana, Chao, Xiaojuan, Ahmadi, Ali Reza, Peiffer, Brandon, Sun, Zhaoli, Sesaki, Hiromi, Li, Tiangang, Wang, Xiaokun, Liu, Wanqing, Bataller, Ramon, Ni, Hong-Min, and Ding, Wen-Xing

Subjects
Hepatology, Article
Abstract

BACKGROUND AND AIMS: Increased megamitochondria formation and impaired mitophagy in hepatocytes have been linked to the pathogenesis of alcohol-associated liver disease (ALD). This study aims to determine the mechanisms by which alcohol consumption increases megamitochondria formation in the pathogenesis of ALD. APPROACH AND RESULTS: Human alcoholic hepatitis (AH) liver samples were used for electron microscopy, histology, and biochemical analysis. Liver-specific dynamin-related protein 1 (DRP1; gene name DNM1L, an essential gene regulating mitochondria fission) knockout (L-DRP1 KO) mice and wild-type mice were subjected to chronic plus binge alcohol feeding. Both human AH and alcohol-fed mice had decreased hepatic DRP1 with increased accumulation of hepatic megamitochondria. Mechanistic studies revealed that alcohol feeding decreased DRP1 by impairing transcription factor EB–mediated induction of DNM1L. L-DRP1 KO mice had increased megamitochondria and decreased mitophagy with increased liver injury and inflammation, which were further exacerbated by alcohol feeding. Seahorse flux and unbiased metabolomics analysis showed alcohol intake increased mitochondria oxygen consumption and hepatic nicotinamide adenine dinucleotide (NAD(+)), acylcarnitine, and ketone levels, which were attenuated in L-DRP1 KO mice, suggesting that loss of hepatic DRP1 leads to maladaptation to alcohol-induced metabolic stress. RNA-sequencing and real-time quantitative PCR analysis revealed increased gene expression of the cGAS–stimulator of interferon genes (STING)–interferon pathway in L-DRP1 KO mice regardless of alcohol feeding. Alcohol-fed L-DRP1 KO mice had increased cytosolic mtDNA and mitochondrial dysfunction leading to increased activation of cGAS-STING-interferon signaling pathways and liver injury. CONCLUSION: Alcohol consumption decreases hepatic DRP1 resulting in increased megamitochondria and mitochondrial maladaptation that promotes AH by mitochondria-mediated inflammation and cell injury.

Published
2022
Full Text
View/download PDF

48. CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis

Author

Genin, Emmanuelle C, Plutino, Morgane, Bannwarth, Sylvie, Villa, Elodie, Cisneros‐Barroso, Eugenia, Roy, Madhuparna, Ortega‐Vila, Bernardo, Fragaki, Konstantina, Lespinasse, Françoise, Pinero‐Martos, Estefania, Augé, Gaëlle, Moore, David, Burté, Florence, Lacas‐Gervais, Sandra, Kageyama, Yusuke, Itoh, Kie, Yu‐Wai‐Man, Patrick, Sesaki, Hiromi, Ricci, Jean‐Ehrland, Vives‐Bauza, Cristofol, and Paquis‐Flucklinger, Véronique

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results