The SLC25A1-p53 mutant crosstalk.

Chris Albanese,Maria Laura Avantaggiati

doi:10.18632/aging.100785

Abstract

The SLC25A1-p53 mutant crosstalk.

Highlights

A second fundamental function of SLC25A1 surprisingly consists in overcoming the glycolytic addiction of tumors, while promoting mitochondrial activity and oxidative phosphorylation, through which SLC25A1 enacts adaptation in response to glucose starvation or mitochondrial respiration injury [5]
This SLC25A1 activity may at first glance appear paradoxical -given that the Warburg effect is considered a hallmark of tumors- recent evidence has challenged the long-standing precept of the glycolytic requirement for tumor proliferation, and "a reversal of the Warburg effect" exists in the tumor-stroma crosstalk [e.g.,5]
In patients affected by Li– Fraumeni syndrome harboring mutations of the p53 gene, mitochondrial respiration is increased in the skeletal muscle associated with high levels of mitochondrial respiratory complexes [6]

Summary

Introduction

The presence of p53 mutations in human cancers, which occurs with a frequency higher than 50%, is a negative prognostic factor predictive of relapse and of resistance to chemo- and radio-therapy, rendering these types of tumors a still unsolved therapeutic challenge. Given that cytoplasmic citrate is the predominant source for lipid synthesis, it is likely that SLC25A1 is involved in this activity of mutp53. A second fundamental function of SLC25A1 surprisingly consists in overcoming the glycolytic addiction of tumors (the Warburg effect), while promoting mitochondrial activity and oxidative phosphorylation, through which SLC25A1 enacts adaptation in response to glucose starvation or mitochondrial respiration injury [5].

Results

Conclusion