Abstract
In this review we discuss the interaction between metabolic stress, mitochondrial dysfunction, and genomic instability. Unrepaired DNA damage in the nucleus resulting from excess accumulation of DNA damages and stalled replication can initiate cellular signaling responses that negatively affect metabolism and mitochondrial function. On the other hand, mitochondrial pathologies can also lead to stress in the nucleus, and cause sensitivity to DNA-damaging agents. These are examples of how hallmarks of cancer and aging are connected and influenced by each other to protect humans from disease.
Highlights
It has been almost two decades since Hanahan and Weinberg for the first time classified the hallmarks of cancer [1]
We will discuss nuclear processes that are dependent on mitochondrial function and intermediate metabolites
During stress and increased energy demand, cells respond by boosting cellular respiration and mitochondrial activity to provide the cells with ATP and NAD+ [12,62]
Summary
It has been almost two decades since Hanahan and Weinberg for the first time classified the hallmarks of cancer [1]. NAD+ and ATP, which can in turn lead to additional metabolic stress and mitochondrial dysfunction (Figure 1) [13,14,15]. Apart from preventing cell cycle progression and the recruitment of DNA repair proteins, these enzymes can modulate mitochondrial function and survival [23,39]. ATM, ATR, and DNA-PK are able to promote survival via the direct phosphorylation of AKT ( known as protein kinase B, PKB) independently of growth factor signaling [22,40,41,42,43]. The mechanism of this interaction is not fully understood [44] This is interesting, as in many cancer cells, the AKT is activated independently of growth factors [45]. Decrease in FOXO activity results in the decrease of mitochondrial biogenesis, mitophagy, autophagy, and lipolysis [49]
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