fig2

Figure 2. UPR^mt signaling pathway and its role in preserving mitochondrial integrity in mammals. UPR^mt acts in the defense against mitochondrial stress through mitochondrial stress-nucleus communication. The unfolded proteins in the matrix and/or IMS initiate the activation of different proteins involved in UPR^mt. Following this signal, the development of this response is initiated through the activation of proteins such as JNK, SIRT3, eIF2α, and ERα, which, in turn send signals to the nucleus to induce UPR^mt via other proteins (e.g., CHOP) and transcription factors (e.g., c-Jun, FOXO3, NRF1, OMI/HTRA2) to promote the transcription of genes involved in halting mitochondrial damage and preserving mitochondria in their healthy state. IMS: Intermembrane space; JNK: Jun N-terminal kinase; SIRT3: Sirtuin 3; eIF2α: eukaryotic translational initiation factor 2α; ER-α: Estrogen receptor α; CHOP: CCAAT/enhancer binding proteins (C/EBP) homologous protein; FOXO3: Forkhead box O3; NRF1: Nuclear respiratory factor 1; OMI/HTRA2: High-temperature protein A2. Created using BioRender (www.app.biorender.com).