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Aberrant activation of Lon protease accelerates TFAM proteolysis and triggers nucleoid dissolution ( Nucleoid destabilization has been documented in a range of conditions outside autoimmunity, including MELAS, Parkinson’s disease, Alzheimer’s disease, aging, and diabetes, in which pathogenic mtDNA mutations, protein aggregates competing with TFAM for DNA binding, or cumulative oxidative and glycative modification of TFAM converge on the same outcome of nucleoid loosening and mtDNA depletion (49)