Mitochondria and cancer.

Abstract

Editorial Proliferating cells such as tumor cells have increased metabolic demands that include ATP, NADPH, lipids, proteins, and nucleotides to allow for a tumor cell to divide into two daughter cells [1]. Tumor cells reprogram their cell metabolism to sustain the increased metabolic demands of cell proliferation. Historically, much attention has focused on glycolysis as the central metabolic pathway important for tumor cell metabolism, an idea that stems from the observation made in 1920s by Otto Warburg that tumor slices consume glucose at a higher rate than normal tissue slices at normal oxygen levels [2]. This high rate of aerobic glycolysis is known as the Warburg effect and can be observed in proliferating tumor cells of cancer patients by the high uptake of the glucose analogue tracer 18-fluorodeoxyglucose (FDG) detected by Positron Emission Tomography (PET) technology [3]. The basis and the advantage of the Warburg effect for proliferating cells such as cancer cells had not been fully resolved until recently. Today, there is consensus that combination of gain of function of oncogenes, loss or tumor suppressor and aberrant activation of signaling pathways downstream of growth factor signaling induce the Warburg effect [4]. This increase in glucose metabolism through glycolysis allows the generation of glycolytic intermediates that funnel into biosynthetic pathways that support the production of NADPH, lipids, proteins and nucleotides [5]. However, the biochemists working on cancer metabolism decades ago realized that glucose metabolism alone could not fully support the de novo production of NADPH, ATP, lipids, nucleotides and proteins required for cell proliferation. Today, it is appreciated that mitochondrial metabolism is also essential for building blocks needed for cell proliferation. For example, phospholipid generation needed for de novo cell membranes in proliferating cells requires fatty acids and glycerol. The glycolytic intermediate dihydroxyacetone