Image: Susanne Krasemann, University Medical Center Hamburg Eppendorf UKE and Mariana Fernandez-Caggiano, The William Harvey Research Institute, Queen Mary University of London.

Rewiring cardiac metabolism after heart failure

Latest Research

  • Article |

    Wei et al. identify the HDL receptor SR-B1 as a host factor that enhances infection of cultured cells with SARS-CoV-2 in the presence of ACE2, thus providing a possible molecular connection between lipoprotein metabolism and COVID-19.

    • Congwen Wei
    • , Luming Wan
    • , Qiulin Yan
    • , Xiaolin Wang
    • , Jun Zhang
    • , Xiaopan Yang
    • , Yanhong Zhang
    • , Chen Fan
    • , Dongyu Li
    • , Yongqiang Deng
    • , Jin Sun
    • , Jing Gong
    • , Xiaoli Yang
    • , Yufei Wang
    • , Xuejun Wang
    • , Jianmin Li
    • , Huan Yang
    • , Huilong Li
    • , Zhe Zhang
    • , Rong Wang
    • , Peng Du
    • , Yulong Zong
    • , Feng Yin
    • , Wanchuan Zhang
    • , Nan Wang
    • , Yumeng Peng
    • , Haotian Lin
    • , Jiangyue Feng
    • , Chengfeng Qin
    • , Wei Chen
    • , Qi Gao
    • , Rui Zhang
    • , Yuan Cao
    •  & Hui Zhong
  • Letter |

    UCP2 is shown in yeast and mammalian cells to transport aspartate out of mitochondria, thus enabling KRAS-mutated pancreatic ductal adenocarcinoma cells to perform glutaminolysis to support cancer growth.

    • Susanna Raho
    • , Loredana Capobianco
    • , Rocco Malivindi
    • , Angelo Vozza
    • , Carmela Piazzolla
    • , Francesco De Leonardis
    • , Ruggiero Gorgoglione
    • , Pasquale Scarcia
    • , Francesca Pezzuto
    • , Gennaro Agrimi
    • , Simona N. Barile
    • , Isabella Pisano
    • , Stephan J. Reshkin
    • , Maria R. Greco
    • , Rosa A. Cardone
    • , Vittoria Rago
    • , Yuan Li
    • , Carlo M. T. Marobbio
    • , Wolfgang Sommergruber
    • , Christopher L. Riley
    • , Francesco M. Lasorsa
    • , Edward Mills
    • , Maria C. Vegliante
    • , Giuseppe E. De Benedetto
    • , Deborah Fratantonio
    • , Luigi Palmieri
    • , Vincenza Dolce
    •  & Giuseppe Fiermonte
  • Article |

    Oncogenic transformation can render cancer cells dependent on aberrant expression of glycolytic enzyme isoforms. Lin et al. describe a novel enolase inhibitor, POMHEX, that can selectively kill ENO1-deleted glioblastomas.

    • Yu-Hsi Lin
    • , Nikunj Satani
    • , Naima Hammoudi
    • , Victoria C. Yan
    • , Yasaman Barekatain
    • , Sunada Khadka
    • , Jeffrey J. Ackroyd
    • , Dimitra K. Georgiou
    • , Cong-Dat Pham
    • , Kenisha Arthur
    • , David Maxwell
    • , Zhenghong Peng
    • , Paul G. Leonard
    • , Barbara Czako
    • , Federica Pisaneschi
    • , Pijus Mandal
    • , Yuting Sun
    • , Rafal Zielinski
    • , Susana Castro Pando
    • , Xiaobo Wang
    • , Theresa Tran
    • , Quanyu Xu
    • , Qi Wu
    • , Yongying Jiang
    • , Zhijun Kang
    • , John M. Asara
    • , Waldemar Priebe
    • , William Bornmann
    • , Joseph R. Marszalek
    • , Ronald A. DePinho
    •  & Florian L. Muller
  • Article |

    Chini et al. demonstrate that CD38+ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38+ affects intracellular NAD+ levels in vivo by hydrolyzing the NAD+ intermediate nicotinamide mononucleotide extracellularly.

    • Claudia C. S. Chini
    • , Thais R. Peclat
    • , Gina M. Warner
    • , Sonu Kashyap
    • , Jair Machado Espindola-Netto
    • , Guilherme C. de Oliveira
    • , Lilian S. Gomez
    • , Kelly A. Hogan
    • , Mariana G. Tarragó
    • , Amrutesh S. Puranik
    • , Guillermo Agorrody
    • , Katie L. Thompson
    • , Kevin Dang
    • , Starlynn Clarke
    • , Bennett G. Childs
    • , Karina S. Kanamori
    • , Micaela A. Witte
    • , Paola Vidal
    • , Anna L. Kirkland
    • , Marco De Cecco
    • , Karthikeyani Chellappa
    • , Melanie R. McReynolds
    • , Connor Jankowski
    • , Tamara Tchkonia
    • , James L. Kirkland
    • , John M. Sedivy
    • , Jan M. van Deursen
    • , Darren J. Baker
    • , Wim van Schooten
    • , Joshua D. Rabinowitz
    • , Joseph A. Baur
    •  & Eduardo N. Chini
  • Article |

    Senescent cells in fat and liver are shown to attract M1-like macrophages with increased expression of the NAD-consuming enzyme CD38, leading to their local accumulation and providing a mechanism for the age-associated decline in tissue NAD+ levels.

    • Anthony J. Covarrubias
    • , Abhijit Kale
    • , Rosalba Perrone
    • , Jose Alberto Lopez-Dominguez
    • , Angela Oliveira Pisco
    • , Herbert G. Kasler
    • , Mark S. Schmidt
    • , Indra Heckenbach
    • , Ryan Kwok
    • , Christopher D. Wiley
    • , Hoi-Shan Wong
    • , Eddy Gibbs
    • , Shankar S. Iyer
    • , Nathan Basisty
    • , Qiuxia Wu
    • , Ik-Jung Kim
    • , Elena Silva
    • , Kaitlyn Vitangcol
    • , Kyong-Oh Shin
    • , Yong-Moon Lee
    • , Rebeccah Riley
    • , Issam Ben-Sahra
    • , Melanie Ott
    • , Birgit Schilling
    • , Morten Scheibye-Knudsen
    • , Katsuhiko Ishihara
    • , Stephen R. Quake
    • , John Newman
    • , Charles Brenner
    • , Judith Campisi
    •  & Eric Verdin
  • Article |

    The PI3K–PTEN signalling pathway is a central regulator of metabolic homeostasis. Brunner et al. find that cell-intrinsic PI3K signalling allows adipose tissue macrophages to buffer obesity-induced lipotoxicity by promoting lipid uptake and catabolism.

    • Julia S. Brunner
    • , Andrea Vogel
    • , Alexander Lercher
    • , Michael Caldera
    • , Ana Korosec
    • , Marlene Pühringer
    • , Melanie Hofmann
    • , Alexander Hajto
    • , Markus Kieler
    • , Lucia Quemada Garrido
    • , Martina Kerndl
    • , Mario Kuttke
    • , Ildiko Mesteri
    • , Maria W. Górna
    • , Marta Kulik
    • , Paulina M. Dominiak
    • , Amanda E. Brandon
    • , Emma Estevez
    • , Casey L. Egan
    • , Florian Gruber
    • , Martina Schweiger
    • , Jörg Menche
    • , Andreas Bergthaler
    • , Thomas Weichhart
    • , Kristaps Klavins
    • , Mark A. Febbraio
    • , Omar Sharif
    •  & Gernot Schabbauer

News & Comment

  • News & Views |

    The restoration of the progressive decline in nicotinamide adenine dinucleotide (NAD+) levels mitigates certain age-associated dysfunctions. A fundamental question is how the NAD+-consuming enzyme CD38 decreases NAD+ levels during ageing. Two new studies by Chini et al. and Covarrubias et al. in this issue of Nature Metabolism show that CD38 expression in macrophages induced by senescence-associated inflammation accounts for the age-related decline in NAD+ levels.

    • Shuai Wu
    •  & Rugang Zhang
  • News & Views |

    A new global measure of cell-to-cell transcriptional variability from single-cell RNA-sequencing data has been developed by Levy et al., on the basis of the transcriptional interrelations between genes. The new variable, termed global coordination level, decreases with age in different organisms and cell types and correlates with high mutational load in cells.

    • Jan Vijg
  • News & Views |

    The heart is an organ with high energy demands and metabolic flexibility, thus allowing for various energy substrates for ATP production under different physiological conditions. Zhang et al., Fernandez-Caggiano et al. and McCommis et al. converge on the mitochondrial pyruvate transporter as a key metabolic hub for the maintenance of cardiac metabolism and a critical determinant of cardiac metabolic plasticity during heart failure.

    • P. Christian Schulze
    •  & Jasmine M. F. Wu
  • Comment |

    Cell culture media are typically selected on the basis of common laboratory practices but have major effects on the validity, reproducibility and physiological relevance of the scientific findings. We provide arguments and quantitative examples of why choosing an appropriate cell culture medium matters, particularly in metabolic studies.

    • Shoval Lagziel
    • , Eyal Gottlieb
    •  & Tomer Shlomi
  • News & Views |

    A recent study by Karunakaran et al. suggests that RIPK1 is important in obesity and related metabolic traits. With genetic variation associated with expression and the risk of obesity, and repression of activity leading to a favourable metabolic profile in an obesogenic model, is there evidence for a potential therapeutic role?

    • Nicholas John Timpson
  • Editorial |

    As the world came to a standstill in the spring of 2020, so did the work on our Focus issue on exercise metabolism and health, which was originally scheduled for publication to coincide with the 2020 Summer Olympic Games.