Proper mitochondrial genome inheritance is important for eukaryotic cell survival. , a protozoan parasite, contains a singular mitochondrial genome, the kinetoplast (k)DNA. The kDNA is anchored to the basal body via the tripartite attachment complex (TAC) to ensure proper segregation. Several components of the TAC have been described; however, the connection of the TAC to the kDNA remains elusive. Here, we characterize the TAC-associated protein TAP110. We find that both depletion and overexpression of TAP110 leads to a delay in the separation of the replicated kDNA networks. Proteome analysis after TAP110 overexpression identified several kDNA-associated proteins that changed in abundance, including a TEX-like protein that dually localizes to the nucleus and the kDNA, potentially linking replication and segregation in the two compartments. The assembly of TAP110 into the TAC region seems to require the TAC but not the kDNA itself; however, once TAP110 has been assembled, it also interacts with the kDNA. Finally, we use ultrastructure expansion microscopy in trypanosomes for the first time, and reveal the precise position of TAP110 between TAC102 and the kDNA, showcasing the potential of this approach.This article has an associated First Person interview with the first author of the paper.
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http://dx.doi.org/10.1242/jcs.254300 | DOI Listing |
Sci Total Environ
January 2025
Department of Twin Research and Genetic Epidemiology, King's College London, 3-4th Floor South Wing Block D, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. Electronic address:
Heavy metals in our direct environment have profound effects on human health and while some are essential for life, others can be toxic. In vivo studies often focus on clinical features caused by overexposure to, or by deprivation of a heavy metal. However, to understand the cellular impact of heavy metals on health, studies in healthy volunteers before symptom onset are needed.
View Article and Find Full Text PDFMol Genet Genomic Med
January 2025
Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Background: Sengers syndrome is an autosomal recessive mitochondrial DNA depletion syndrome characterized by hypertrophic cardiomyopathy, congenital cataracts, skeletal myopathy, exercise intolerance, and lactic acidosis. Dysfunction of acylglycerol kinase (AGK) is responsible for the disease, and several AGK gene variants have been reported.
Methods: We employed a comprehensive genomic analysis approach, including whole-genome sequencing and RNA sequencing, combined with various bioinformatics tools.
Curr Med Chem
January 2025
Laboratory of Angiopathology Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, 125315, Moscow, Russia.
This review discusses the possibility of inheritance of some diseases through mutations in mitochondrial DNA. These are examples of many mitochondrial diseases that can be caused by mutations in mitochondrial DNA. Symptoms and severity can vary widely depending on the specific mutation and affected tissues.
View Article and Find Full Text PDFTransl Cancer Res
December 2024
Department of Biomedical Engineering, School of Life Sciences, Guangxi Medical University, Nanning, China.
Background: The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC.
View Article and Find Full Text PDFBMC Cancer
January 2025
Department of Otorhinolaryngology, Shenzhen Key Laboratory of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital, Shenzhen Institute of Otorhinolaryngology, No. 3004 Longgang Avenue, Shenzhen, Guangdong, China.
Background: To investigate the role of the translocase of the outer mitochondrial membrane 40 (TOM40) in oral squamous cell carcinoma (OSCC) with the aim of identifying new biomarkers or potential therapeutic targets.
Methods: TOM40 expression level in OSCC was evaluated using datasets downloaded from The Cancer Genome Atlas (TCGA), as well as clinical data. The correlation between TOM40 expression level and the clinicopathological parameters and survival were analyzed in TCGA.
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