In animals, mitochondria are mainly organised into an interconnected tubular network extending across the cell along a cytoskeletal scaffold. Mitochondrial fission and fusion, as well as distribution along cytoskeletal tracks, are counterbalancing mechanisms acting in concert to maintain a mitochondrial network tuned to cellular function. Balanced mitochondrial dynamics permits quality control of the network including biogenesis and turnover, and distribution of mitochondrial DNA, and is linked to metabolic status. Cellular and organismal health relies on a delicate balance between fission and fusion, and large rearrangements in the mitochondrial network can be seen in response to cellular insults and disease. Indeed, dysfunction in the major components of the fission and fusion machineries including dynamin-related protein 1 (DRP1), mitofusins 1 and 2 (MFN1, MFN2) and optic atrophy protein 1 (OPA1) and ensuing imbalance of mitochondrial dynamics can lead to neurodegenerative disease. Altered mitochondrial dynamics is also seen in more common diseases. In this review, the machinery involved in mitochondrial dynamics and their dysfunction in disease will be discussed.
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http://dx.doi.org/10.1002/1873-3468.14077 | DOI Listing |
Adv Mater
January 2025
Príncipe Felipe Research Center, Polymer Therapeutics Lab., Valencia, 46012, Spain.
Mitochondria play critical roles in regulating cell fate, with dysfunction correlating with the development of multiple diseases, emphasizing the need for engineered nanomedicines that cross biological barriers. Said nanomedicines often target fluctuating mitochondrial properties and/or present inefficient/insufficient cytosolic delivery (resulting in poor overall activity), while many require complex synthetic procedures involving targeting residues (hindering clinical translation). The synthesis/characterization of polypeptide-based cell penetrating diblock copolymers of poly-L-ornithine (PLO) and polyproline (PLP) (PLO-PLP, n:m ratio 1:3) are described as mitochondria-targeting nanocarriers.
View Article and Find Full Text PDFCancers (Basel)
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Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining tumor control, a phenomenon termed the FLASH effect. Despite promising outcomes, the precise mechanisms underlying the FLASH effect remain elusive and are a focal point of current research.
View Article and Find Full Text PDFInt J Mol Sci
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Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides a comprehensive analysis of the effects of PSMs on mitochondrial health, with particular emphasis on their therapeutic potential. Emerging evidence shows that these metabolites improve mitochondrial function by reducing oxidative stress, promoting mitochondrial biogenesis, and regulating key processes such as apoptosis and mitophagy.
View Article and Find Full Text PDFInt J Mol Sci
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Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Ovarian aging significantly impacts female fertility, with mitochondrial dysfunction emerging as a key factor. This study investigated the effects of recombinant follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on mitochondrial function and metabolism in aging female reproductive cells. Human granulosa cells (HGL5) were treated with FSH/LH or not.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Hefei National Laboratory for Physical Sciences at the Microscale, MOE Key Laboratory for Membrane-Less Organelles & Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
Mitochondrial function is essential for synaptic function. ATAD1, an AAA+ protease involved in mitochondrial quality control, governs fission-fusion dynamics within the organelle. However, the distribution and functional role of ATAD1 in neurons remain poorly understood.
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