Ting Liang, Belinda Bernal, Wenbo Qi, Yuji Ikeno, Adam B Salmon, Daisy Kwok, Joel Michalek, Mai Zhou, Yidong Bai
{"title":"Robust assembly of electron transfer chain in the brain of naked mole-rats during aging.","authors":"Ting Liang, Belinda Bernal, Wenbo Qi, Yuji Ikeno, Adam B Salmon, Daisy Kwok, Joel Michalek, Mai Zhou, Yidong Bai","doi":"10.61747/0ifp.202408002","DOIUrl":"10.61747/0ifp.202408002","url":null,"abstract":"<p><p>Naked mole-rats (NMR, <i>Heterocephalus glaber</i>) are the longest-lived rodent species, with a maximum life span of more than 30 years. These long-lived mammals exhibit delayed aging phenotypes and resistance to age-related pathologies including neurodegeneration. Multiple regulatory pathways have been proposed for the anti-aging mechanisms in NMR including enhanced mitochondrial function and suppressed oxidative stress. In this study, we investigated the assembly of the electron transfer chain (ETC) which constitutes the structural base for the regulation of both oxidative phosphorylation and the production of reactive oxygen species (ROS), in brains from young and old NMR and C57BL/6 mice. While ETC assembly declined with aging in C57BL/6 mice, we found that NMR display a robust respiratory chain assembly at older ages in both males and females. Among them, individual complex IV and supercomplexes containing complex I and III or complex III and IV showed the most pronounced differences between two species. Our results indicate that a preserved robust assembly of ETC during aging contributes to enhanced mitochondrial oxidative phosphorylation and suppressed oxidative stress, which may contribute to the longevity and resistance to age-related pathologies in NMR.</p>","PeriodicalId":520489,"journal":{"name":"Organelle (Tucson, Ariz.)","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Organelle abnormalities in Alzheimer's disease.","authors":"Ju Gao, Lauren Vicuna, Xinglong Wang","doi":"10.61747/0ifp.202503005","DOIUrl":"10.61747/0ifp.202503005","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common cause of dementia, pathologically characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles. While these pathological hallmarks remain central to our understanding of AD, they do not fully explain the complex cellular failures observed throughout the disease course. Neurons are highly specialized and polarized cells that depend on an integrated and dynamic network of specialized subcellular compartments named organelles to maintain structure, metabolism, and communication. Given these critical roles, organelle dysfunction is increasingly recognized as a key contributor to AD pathogenesis. Structural and functional impairments in conventional organelles, including mitochondria, endoplasmic reticulum (ER), lysosomes, Golgi apparatus, and peroxisomes, are consistently observed in AD brains and experimental models. These impairments are believed to cause energy failure, disrupted proteostasis, intracellular trafficking defects, and elevated oxidative and ER stress. In parallel, abnormalities in membraneless organelles (MLOs) further compromise RNA regulation, protein synthesis, and cellular stress responses. Additionally, perturbed communication between organelles, such as at mitochondria-associated ER membranes (MAMs), lipid droplets, and primary cilia, further exacerbates signaling imbalances and neuronal vulnerability. In this review, we not only provide a comprehensive overview of abnormalities in both membrane-bound and membraneless organelles in AD, emphasizing how their dysfunction contributes to cellular stress, impaired homeostasis, and neurodegeneration, but also discuss how disruptions in organelles intersect with amyloid, tau, and other AD-associated pathologies to intensify disease progression. A deeper understanding of organelle dysfunction in AD may provide new mechanism insights and advance the development of effective disease modifying interventions.</p>","PeriodicalId":520489,"journal":{"name":"Organelle (Tucson, Ariz.)","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12523919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stress Induced Mitochondrial Hyperfusion (SIMH): A Concise Review on SIMH in Neurodegenerative Disorders and Other Diseases.","authors":"Jeffrey D Brown, Mei-Zhen Cui, Xuemin Xu","doi":"10.61747/0ifp.202503002","DOIUrl":"10.61747/0ifp.202503002","url":null,"abstract":"<p><p>Mitochondria are critical for cell health, and damaged or dysfunctional mitochondria have been strongly linked to various human diseases, particularly neurodegenerative disorders. Mitochondrial function is regulated by several mechanisms, including the regulation of mitochondrial shape, size, number, and morphology. Mitochondria constantly fuse together and separate; this fusion and fission process is known as mitochondrial dynamics. These mitochondrial dynamics are modulated in response to various stimuli, and recent reports have demonstrated that mitochondria undergo hyperfusion under mild to moderate stress conditions, resulting in the formation of elongated filaments. This phenomenon is referred to as stress induced mitochondrial hyperfusion (SIMH). SIMH is associated with enhanced protection of mitochondria and improved cell viability under stress conditions. The induction of hyperfusion can be triggered by diverse stressors, each with distinct and unique mechanisms. This mini review will focus on these stressors and their corresponding mechanisms, as well as the subsequent effects on mitochondrial and cell health. Additionally, disease models which demonstrate a correlation between specific disease-related stress conditions and mitochondrial hyperfusion are discussed.</p>","PeriodicalId":520489,"journal":{"name":"Organelle (Tucson, Ariz.)","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wanli Smith, Mali Jiang, Jazlynn Meza, Gabriela Mercado
{"title":"Targeting inflammasome pathway towards therapeutics of neurodegenerative diseases.","authors":"Wanli Smith, Mali Jiang, Jazlynn Meza, Gabriela Mercado","doi":"10.61747/0ifp.202503001","DOIUrl":"10.61747/0ifp.202503001","url":null,"abstract":"<p><p>Inflammasome, an intracellular protein complex, is a crucial regulator of the innate immune response defending against harmful insults. Increasing evidence indicates that activation of inflammasome pathway in brain cells plays a significant pathological role in neurodegenerative diseases. Targeting this pathway offers a promising strategy for developing novel treatments. Here, we review the wide-ranging involvement of inflammasome activation in neurodegenerative diseases and highlight current therapeutic strategies targeting this critical pathway.</p>","PeriodicalId":520489,"journal":{"name":"Organelle (Tucson, Ariz.)","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12636706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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