Triple negative breast cancer (TNBC) is one of the most aggressive cancer subtypes in which 35% of patients suffer tumor recurrence. Increasing evidence suggests that this high recurrence is due to the presence of tumor cells with stem cell-like characteristics (CSC). It has been reported that the acquisition of a CSC phenotype correlates with an increased expression of the androgen receptor (AR). We previously showed that AR regulates the expression of the transcription factor RUNX1 in AR+ TNBC cell lines and PDX. RUNX1 expression correlates with a poor prognosis in TNBC patients and we reported that it participates in the CSC generation and chemoresistance in TNBC. Recent evidence indicates that CSC presents an imbalance towards the use of mitochondrial oxidative phosphorylation producing functional and morphological reprogramming. The AR and RUNX1 signaling pathways have been associated with mitophagy and mitochondrial function in some cancer models. Here we show, for the first time, that inhibition of RUNX transcriptional activity with the commercial inhibitor AI-10-104 leads to mitochondria reorganization and fragmentation. Moreover, MDA-MB-453 and SUM-159PT cells lines treated with AI-10-104 have an accumulation of the immature isoform of the mitochondrial protein frataxin (FXN) with the consequent decrease of the mature and functional isoform. FXN is a small protein involved in the biosynthesis of Fe-S clusters and their transfer to key cell metabolism proteins; alterations in FXN leads to neurodegenerative and metabolic disorders. On the other hand, we didn’t find changes in the expression of the mitophagy genes BECLIN1 and ATG7, suggesting that it would not be involved at these temporal points. We hypothesize that the AR/RUNX signaling pathway participate in mitochondrial reprogramming favoring the survival of TNBC cells, and our aim is to characterize the role of AR and RUNX1 as potential new modulators of mitochondrial metabolism and dynamics in AR+ TNBC.