Given the vital role of Lon to maintain TFAM stability and mtDNA content under mitochondrial dysfunction by proper protein homoeostasis, the finding of specific Lon protease inhibitors or activators will allow us to manipulate the TFAM and mtDNA level by regulating the activity of Lon protease, which will further facilitate the treatment of cancer, as well as neurodegenerative diseases related to protein aggregation in mitochondria. Here, TFAM is linked to cancer.