Intersections between mitochondrial sirtuin signaling and tumor cell metabolism

Abstract

Cancer cells use glucose and glutamine to facilitate cell growth and proliferation, a process coined “metabolic reprograming” – an emerging hallmark of cancer. Inside the cell, these nutrients synergize to produce metabolic building blocks, such as nucleic acids, lipids and proteins, as well as energy (ATP), glutathione and reducing equivalents (NADPH), required for survival, growth and proliferation. Intense research aimed at understanding the underlying cause of the metabolic rewiring has revealed that established oncogenes and tumor suppressors involved in signaling alter cellular metabolism to contribute to the transition from a normal quiescent cell to a rapidly proliferating cancer cell. Likewise, bona fide metabolic sensors are emerging as regulators of tumorigenesis. This review will focus on one such family of sensors, sirtuins, which utilize NAD⁺ as a cofactor to catalyze deacetylation, deacylation and ADP-ribosylation of their protein substrates. In this review, we will enumerate how cancer cell metabolism is different from a normal quiescent cell and highlight the emerging role of mitochondrial sirtuin signaling in the regulation of tumor metabolism.

• Antioxidants
• glutamine metabolism
• metabolic reprograming
• signaling pathways
• Warburg effect

Declaration of interest

Karina N. Gonzalez was supported by the Paul & Daisy Soros Fellowship for New Americans. Jaewon Lee was supported by HHMI. Marcia C. Haigis, PhD, was supported by an American Cancer Society Research Scholar Grant, the National Institutes of Health (NIH) Grant AG032375, and the Glenn Foundation for Medical Research.