Fig. 3

The mitonuclear communication. a Noncoding RNA in nucleus-mitochondria regulation (using lnc RMRP as an example). The lnc RMRP transcribed in nucleus is translocated in the mitochondria and targets the mtDNA, while the mtDNA encoding small noncoding RNA (snmtRNA) can be transferred to the nucleus. Both processes require the cooperation of RNA-binding proteins such as HuR and GRSF1. b Anterograde regulation. Different cytoplasmic stressors initiate several signaling pathways and activate the same co-activator PGC1α, which subsequently stimulates different transcription factors and nuclear receptors as shown in Fig. 3. The downstream signaling of these transcription factors and nuclear receptors regulates mitochondrial biogenesis. Not all transcription factors, co-activators, and co-repressors are shown in Fig. 3 (see Refs [119, 120]). c Retrograde regulation. Retrograde signaling is triggered by OXPHOS dysfunction and mtDNA defects, which result in the loss of mitochondria potential. The retrograde pathway involves Cn-calcium signaling, AMPK signaling, and activation of molecules such as HnRNP A2, which is a cancer hallmark. Retrograde regulation also increases the expression of certain epigenetic modulators that regulate the nuclear epigenome