@article{12747,
  abstract     = {Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing.},
  author       = {Cikes, Domagoj and Elsayad, Kareem and Sezgin, Erdinc and Koitai, Erika and Ferenc, Torma and Orthofer, Michael and Yarwood, Rebecca and Heinz, Leonhard X. and Sedlyarov, Vitaly and Darwish-Miranda, Nasser and Taylor, Adrian and Grapentine, Sophie and al-Murshedi, Fathiya and Abot, Anne and Weidinger, Adelheid and Kutchukian, Candice and Sanchez, Colline and Cronin, Shane J. F. and Novatchkova, Maria and Kavirayani, Anoop and Schuetz, Thomas and Haubner, Bernhard and Haas, Lisa and Hagelkruys, Astrid and Jackowski, Suzanne and Kozlov, Andrey and Jacquemond, Vincent and Knauf, Claude and Superti-Furga, Giulio and Rullman, Eric and Gustafsson, Thomas and McDermot, John and Lowe, Martin and Radak, Zsolt and Chamberlain, Jeffrey S. and Bakovic, Marica and Banka, Siddharth and Penninger, Josef M.},
  issn         = {2522-5812},
  journal      = {Nature Metabolism},
  keywords     = {Cell Biology, Physiology (medical), Endocrinology, Diabetes and Metabolism, Internal Medicine},
  pages        = {495--515},
  publisher    = {Springer Nature},
  title        = {{PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing}},
  doi          = {10.1038/s42255-023-00766-2},
  volume       = {5},
  year         = {2023},
}

@article{7711,
  abstract     = {The nature and extent of mitochondrial DNA variation in a population and how it affects traits is poorly understood. Here we resequence the mitochondrial genomes of 169 Drosophila Genetic Reference Panel lines, identifying 231 variants that stratify along 12 mitochondrial haplotypes. We identify 1,845 cases of mitonuclear allelic imbalances, thus implying that mitochondrial haplotypes are reflected in the nuclear genome. However, no major fitness effects are associated with mitonuclear imbalance, suggesting that such imbalances reflect population structure at the mitochondrial level rather than genomic incompatibilities. Although mitochondrial haplotypes have no direct impact on mitochondrial respiration, some haplotypes are associated with stress- and metabolism-related phenotypes, including food intake in males. Finally, through reciprocal swapping of mitochondrial genomes, we demonstrate that a mitochondrial haplotype associated with high food intake can rescue a low food intake phenotype. Together, our findings provide new insight into population structure at the mitochondrial level and point to the importance of incorporating mitochondrial haplotypes in genotype–phenotype relationship studies.},
  author       = {Bevers, Roel P. J. and Litovchenko, Maria and Kapopoulou, Adamandia and Braman, Virginie S. and Robinson, Matthew Richard and Auwerx, Johan and Hollis, Brian and Deplancke, Bart},
  issn         = {2522-5812},
  journal      = {Nature Metabolism},
  number       = {12},
  pages        = {1226--1242},
  publisher    = {Springer Nature},
  title        = {{Mitochondrial haplotypes affect metabolic phenotypes in the Drosophila Genetic Reference Panel}},
  doi          = {10.1038/s42255-019-0147-3},
  volume       = {1},
  year         = {2019},
}