4.6 Review

Role of Copper on Mitochondrial Function and Metabolism

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.711227

Keywords

mitochondria; copper; metabolic reprograming; hematopoietic stem cells (HSCs); cancer; ROS; proliferation; differentiation

Funding

  1. National Agency of Investigation and Development (ANID), Chile by FONDECYT program
  2. Millenium Institute on Immunology and Immunotherapy

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Copper is crucial for various life processes such as energy metabolism and oxidative stress management in eukaryotic organisms. Dysregulation of copper levels can lead to diseases like anemia and cancer, prompting research into potential therapeutic interventions targeting copper metabolism. This review explores the role of copper in cellular function, metabolic reprogramming, and cancer biology, highlighting its importance in the field of regenerative medicine and oncology.
Copper is essential for life processes like energy metabolism, reactive oxygen species detoxification, iron uptake, and signaling in eukaryotic organisms. Mitochondria gather copper for the assembly of cuproenzymes such as the respiratory complex IV, cytochrome c oxidase, and the antioxidant enzyme superoxide dismutase 1. In this regard, copper plays a role in mitochondrial function and signaling involving bioenergetics, dynamics, and mitophagy, which affect cell fate by means of metabolic reprogramming. In mammals, copper homeostasis is tightly regulated by the liver. However, cellular copper levels are tissue specific. Copper imbalances, either overload or deficiency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity. Consistently, new pharmacological developments have been addressed to reduce or exacerbate copper levels as potential cancer therapies. This review goes over the copper source, distribution, cellular uptake, and its role in mitochondrial function, metabolic reprograming, and cancer biology, linking copper metabolism with the field of regenerative medicine and cancer.

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