The induction of the mitochondrial unfolded protein response (UPR) results in increased transcription of the gene encoding the mitochondrial chaperone HSP70. We systematically screened the C. elegans genome and identified 171 genes that, when knocked down, induce the expression of an hsp-6 HSP70 reporter and encode mitochondrial proteins. These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented). Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence, decreased protein import into mitochondria. In addition, it induces UPR in a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPR and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.
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http://dx.doi.org/10.1016/j.celrep.2019.07.049 | DOI Listing |
Biochim Biophys Acta Bioenerg
January 2025
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
Mitochondrial dysfunction and increased reactive oxygen species (ROS) generation play an import role in different human pathologies. In this context, mitochondrial targeting of potentially protective antioxidants by their coupling to the lipophilic triphenylphosphonium cation (TPP) is widely applied. Employing a six‑carbon (C) linker, we recently demonstrated that mitochondria-targeted phenolic antioxidants derived from gallic acid (AntiOxBEN) and caffeic acid (AntiOxCIN) counterbalance oxidative stress in primary human skin fibroblasts by activating ROS-protective mechanisms.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL) , Heidelberg, Germany.
How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over 2 h. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes, and are sufficient to build the first interphase TAD structures.
View Article and Find Full Text PDFJ Neurosci
January 2025
Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;
Huntington's disease (HD), a neurodegenerative disease, affects approximately 30,000 people in the United States, with 200,000 more at risk. Mitochondrial dysfunction caused by mutant huntingtin (mHTT) drives early HD pathophysiology. mHTT binds the translocase of mitochondrial inner membrane (TIM23) complex, inhibiting mitochondrial protein import and altering the mitochondrial proteome.
View Article and Find Full Text PDFFront Plant Sci
December 2024
Department of Animal Biology, Soil Science and Geology, University of La Laguna, San Cristóbal de La Laguna, Spain.
The scarcity, unstable nutritional quality and environmental cost of imported forages in arid insular regions like Fuerteventura in the Canary Islands (Spain) need exploring sustainable local alternatives. This study evaluated the nutritional quality of twelve native and endemic plant species categorized into legumes, grasses, and a mixed group, cultivated under controlled conditions. The bromatological profiles, focusing on fiber, protein, lipids, and minerals, showed significant differences among plants in key parameters of forage quality: neutral detergent fiber (NDF; 24.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Colon cancer remains a significant health burden globally, necessitating deeper investigation. Identification and targeting of prognostic markers can significantly improve the current therapeutic approaches for colon cancer. The differential nuclear transport (import and export) of cellular proteins, plays an important role in tumor progression.
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