In addition to the UPRmt initiated by events occurring in the mitochondrial matrix, Germain and Papa described another UPRmt model triggered by mitochondrial IMS protein aggregate accumulations, which caused the overexpression of a mutant form of endonuclease G (EndoG-N174A) in breast cancer MCF-7 cells, a condition that increases HTRA2/OMI protein abundance (a mitochondria-located serine protease that can be released by mitochondria during apoptosis) [85], NRF1 expression, and enhanced proteasome activity [78]. The gene discussed is HTRA2; the disease is breast cancer.