@phdthesis{Bertero2022,
  author    = {Bertero, Edoardo},
  title     = {Mechano-energetic uncoupling in Barth syndrome cardiomyopathy},
  doi       = {10.25972/OPUS-25517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255176},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this Doctoral Thesis we investigated the consequences of perturbed mitochondrial calcium handling in the context of a rare human disease, Barth syndrome, in which the altered phospholipid composition of the inner mitochondrial membrane affects the structural organization of several protein complexes, including the mitochondrial calcium uniporter. We discovered that loss of the mitochondrial calcium uniporter in cardiac, but not skeletal muscle mitochondria hinders the calcium-induced adaptation of mitochondrial oxidative metabolism during workload transitions. This mechano-energetic uncoupling impairs the physiological increase in contractile force during physical exercise and might predispose Barth syndrome patients to the development of arrhythmias.},
  language  = {en}
}
@article{SacchettoSequeiraBerteroetal.2019,
  author    = {Sacchetto, Claudia and Sequeira, Vasco and Bertero, Edoardo and Dudek, Jan and Maack, Christoph and Calore, Martina},
  title     = {Metabolic Alterations in Inherited Cardiomyopathies},
  series = {Journal of Clinical Medicine},
  volume    = {8},
  journal   = {Journal of Clinical Medicine},
  number    = {12},
  issn      = {2077-0383},
  doi       = {10.3390/jcm8122195},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193806},
  year      = {2019},
  abstract  = {The normal function of the heart relies on a series of complex metabolic processes orchestrating the proper generation and use of energy. In this context, mitochondria serve a crucial role as a platform for energy transduction by supplying ATP to the varying demand of cardiomyocytes, involving an intricate network of pathways regulating the metabolic flux of substrates. The failure of these processes results in structural and functional deficiencies of the cardiac muscle, including inherited cardiomyopathies. These genetic diseases are characterized by cardiac structural and functional anomalies in the absence of abnormal conditions that can explain the observed myocardial abnormality, and are frequently associated with heart failure. Since their original description, major advances have been achieved in the genetic and phenotype knowledge, highlighting the involvement of metabolic abnormalities in their pathogenesis. This review provides a brief overview of the role of mitochondria in the energy metabolism in the heart and focuses on metabolic abnormalities, mitochondrial dysfunction, and storage diseases associated with inherited cardiomyopathies.},
  language  = {en}
}
@article{SchwemmleinMaackBertero2022,
  author    = {Schwemmlein, Julia and Maack, Christoph and Bertero, Edoardo},
  title     = {Mitochondria as therapeutic targets in heart failure},
  series = {Current Heart Failure Reports},
  volume    = {19},
  journal   = {Current Heart Failure Reports},
  number    = {2},
  doi       = {10.1007/s11897-022-00539-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324015},
  pages     = {27-37},
  year      = {2022},
  abstract  = {Purpose of Review We review therapeutic approaches aimed at restoring function of the failing heart by targeting mitochondrial reactive oxygen species (ROS), ion handling, and substrate utilization for adenosine triphosphate (ATP) production. Recent Findings Mitochondria-targeted therapies have been tested in animal models of and humans with heart failure (HF). Cardiac benefits of sodium/glucose cotransporter 2 inhibitors might be partly explained by their effects on ion handling and metabolism of cardiac myocytes. Summary The large energy requirements of the heart are met by oxidative phosphorylation in mitochondria, which is tightly regulated by the turnover of ATP that fuels cardiac contraction and relaxation. In heart failure (HF), this mechano-energetic coupling is disrupted, leading to bioenergetic mismatch and production of ROS that drive the progression of cardiac dysfunction. Furthermore, HF is accompanied by changes in substrate uptake and oxidation that are considered detrimental for mitochondrial oxidative metabolism and negatively affect cardiac efficiency. Mitochondria lie at the crossroads of metabolic and energetic dysfunction in HF and represent ideal therapeutic targets.},
  language  = {en}
}
@article{AmeriSchiattarellaCrottietal.2020,
  author    = {Ameri, Pietro and Schiattarella, Gabriele Giacomo and Crotti, Lia and Torchio, Margherita and Bertero, Edoardo and Rodolico, Daniele and Forte, Maurizio and Di Mauro, Vittoria and Paolillo, Roberta and Chimenti, Cristina and Torella, Daniele and Catalucci, Daniele and Sciarretta, Sebastiano and Basso, Cristina and Indolfi, Ciro and Perrino, Cinzia},
  title     = {Novel basic science insights to improve the management of heart failure: Review of the working group on cellular and molecular biology of the heart of the Italian Society of Cardiology},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21041192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285085},
  year      = {2020},
  abstract  = {Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.},
  language  = {en}
}
@article{WagnerBerteroNickeletal.2020,
  author    = {Wagner, Michael and Bertero, Edoardo and Nickel, Alexander and Kohlhaas, Michael and Gibson, Gary E. and Heggermont, Ward and Heymans, Stephane and Maack, Christoph},
  title     = {Selective NADH communication from α-ketoglutarate dehydrogenase to mitochondrial transhydrogenase prevents reactive oxygen species formation under reducing conditions in the heart},
  series = {Basic Research in Cardiology},
  volume    = {115},
  journal   = {Basic Research in Cardiology},
  issn      = {0300-8428},
  doi       = {10.1007/s00395-020-0815-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234907},
  year      = {2020},
  abstract  = {In heart failure, a functional block of complex I of the respiratory chain provokes superoxide generation, which is transformed to H\(_2\)O\(_2\) by dismutation. The Krebs cycle produces NADH, which delivers electrons to complex I, and NADPH for H\(_2\)O\(_2\) elimination via isocitrate dehydrogenase and nicotinamide nucleotide transhydrogenase (NNT). At high NADH levels, α-ketoglutarate dehydrogenase (α-KGDH) is a major source of superoxide in skeletal muscle mitochondria with low NNT activity. Here, we analyzed how α-KGDH and NNT control H\(_2\)O\(_2\) emission in cardiac mitochondria. In cardiac mitochondria from NNT-competent BL/6N mice, H\(_2\)O\(_2\) emission is equally low with pyruvate/malate (P/M) or α-ketoglutarate (α-KG) as substrates. Complex I inhibition with rotenone increases H2O2 emission from P/M, but not α-KG respiring mitochondria, which is potentiated by depleting H\(_2\)O\(_2\)-eliminating capacity. Conversely, in NNT-deficient BL/6J mitochondria, H2O2 emission is higher with α-KG than with P/M as substrate, and further potentiated by complex I blockade. Prior depletion of H\(_2\)O\(_2\)-eliminating capacity increases H\(_2\)O\(_2\) emission from P/M, but not α-KG respiring mitochondria. In cardiac myocytes, downregulation of α-KGDH activity impaired dynamic mitochondrial redox adaptation during workload transitions, without increasing H\(_2\)O\(_2\) emission. In conclusion, NADH from α-KGDH selectively shuttles to NNT for NADPH formation rather than to complex I of the respiratory chain for ATP production. Therefore, α-KGDH plays a key role for H\(_2\)O\(_2\) elimination, but is not a relevant source of superoxide in heart. In heart failure, α-KGDH/NNT-dependent NADPH formation ameliorates oxidative stress imposed by complex I blockade. Downregulation of α-KGDH may, therefore, predispose to oxidative stress in heart failure.},
  language  = {en}
}