Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells

In the citing paper

“The availability of NAD+ as an electron acceptor enables aspartate synthesis through aspartate aminotransferase and rescues the proliferation of cultured cells with dysfunctions or inhibition of the electron transport system [16,17].”

In the citing paper

“Despite the prevalence of glycolysis, mitochondrial respiration remains important in proliferating cells, allowing the production of biosynthetic precursors and the generation of electron acceptors that enable aspartate synthesis, for example [9,16,17].”

In the citing paper

“Genetic or epigenetic silencing of ASS1 expression provides an advantage to tumor cells by allowing them to preserve cellular aspartate (Rabinovich et al., 2015), a poorly transported nutrient that can be a critical output of the TCA cycle to support de novo nucleotide synthesis and cell proliferation (Birsoy et al., 2015; Sullivan et al., 2015).”

In the citing paper

“However, mitochondrial ATP production appears dispensable for many proliferating cells (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”

In the citing paper

“Instead, respiration serves an alternative anabolic role for proliferating cells by regenerating the oxidized form of nicotinamide adenine dinucleotide (NAD+) from the reduced form (NADH) (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”

In the citing paper

“For example, eliminating environmental serine, limiting aspartate synthesis via mitochondrial inhibition, and ablating the mitochondrial folate pathway impairs purine biosynthesis (Ducker et al., 2016; Labuschagne et al., 2014; Sullivan et al., 2015).”

In the citing paper

“Additionally, glutamine-derived aspartate plays a crucial role in hypoxic environments or environments with electron transport chain (ETC) impairment28.”

In the citing paper

“Aspartate, which is derived from the transamination of glutamine to form glutamate, participates in pyrimidine and purine biosynthesis28.”

In the citing paper

“Upon ETC dysfunction, the cytosolic steps of the malate–aspartate shuttle can reverse to produce, rather than consume, cytosolic aspartate (42, 43).”

In the citing paper

“Aspartate is used to support protein and nucleotide synthesis in proliferating cells and sustains proliferation in the face of OXPHOS impairment (214).”

In the citing paper

“Time-restricted feeding restores both cycling of metabolic regulators such as cAMP response element-binding protein, mTOR and AMPK, and circadian clock gene expression (214).”

In the citing paper

“In fact, aspartate biosynthesis has recently been shown to be critically dependent upon a cell’s ability to conduct oxidative phosphorylation (Birsoy et al., 2015; Sullivan et al., 2015).”