Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM)

Yuichi Matsushima, Yu Ichi Goto, Laurie S. Kaguni

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)

Abstract

Lon is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. Although a role for Lon in mitochondrial biogenesis has been proposed, the mechanistic basis is unclear. Here, we demonstrate a role for Lon in mtDNA metabolism. An RNA interference (RNAi) construct was designed that reduces Lon to less than 10% of its normal level in Drosophila Schneider cells. RNAi knockdown of Lon results in increased abundance of mitochondrial transcription factor A (TFAM) and mtDNA copy number. In a corollary manner, overexpression of Lon reduces TFAMlevels and mtDNA copy number. Notably, induction of mtDNA depletion in Lon knockdown cells does not result in degradation of TFAM, thereby causing a dramatic increase in the TFAM:mtDNA ratio. The increased TFAM:mtDNA ratio in turn causes inhibition of mitochondrial transcription. We conclude that Lon regulates mitochondrial transcription by stabilizing the mitochondrial TFAM: mtDNA ratio via selective degradation of TFAM.

Original languageEnglish
Pages (from-to)18410-18415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number43
DOIs
Publication statusPublished - Oct 26 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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