Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans

@article{Dingler2020TwoAC,
  title={Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans},
  author={Felix A. Dingler and Meng Wang and Anfeng Mu and Christopher L Millington and Nina Oberbeck and Sam Watcham and Lucas B Pontel and A. Kamimae-Lanning and Fr{\'e}d{\'e}ric Langevin and Camille Nadler and R. Cordell and P. S. Monks and Rui Yu and N. Wilson and A. Hira and K. Yoshida and Minako Mori and Y. Okamoto and Y. Okuno and H. Muramatsu and Y. Shiraishi and Masayuki Kobayashi and T. Moriguchi and T. Osumi and M. Kato and S. Miyano and E. Ito and S. Kojima and H. Yabe and M. Yabe and K. Matsuo and S. Ogawa and B. G{\"o}ttgens and Michael R G Hodskinson and M. Takata and K. Patel},
  journal={Molecular Cell},
  year={2020},
  volume={80},
  pages={996 - 1012.e9}
}
Summary Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes. We find that mice lacking two aldehyde detoxifying enzymes, mitochondrial ALDH2 and cytoplasmic ADH5, have greatly shortened lifespans and develop leukemia. Hematopoiesis is disrupted profoundly, with a reduction of hematopoietic stem cells and common lymphoid progenitors causing a severely depleted acquired immune system. We show that formaldehyde is a common substrate of… Expand
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