PARIS-DJ-1 Interaction Regulates Mitochondrial Functions in Cardiomyocytes, Which Is Critically Important in Cardiac Hypertrophy.

Dibyanti Mukherjee, Vivek Chander, Arun Bandyopadhyay

Molecular and cellular biology 2020 Dec 21

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Mitochondrial dysfunction is one of the major pathological attributes of cardiac hypertrophy and is associated with reduced expression of PGC1α in cardiomyocytes. However, the transcriptional regulation of PGC1α remains elusive. Here, we show that parkin interacting substrate (PARIS), a KRAB zinc finger protein, prevented PGC1α transcription despite the induction of cardiomyocytes with hypertrophic stimuli. Moreover, PARIS expression and its nuclear localization are enhanced in hypertrophy both in vitro and in vivo Knocking down PARIS resulted in mitochondrial biogenesis and improved respiration and other biochemical features that were compromised during hypertrophy. Furthermore, a PARIS-dependent proteome showed exclusive binding of a deSUMOylating protein called DJ-1 to PARIS in control cells, while this interaction is completely abrogated in hypertrophied cells. We further demonstrate that proteasomal degradation of DJ-1 under oxidative stress led to augmented PARIS SUMOylation and consequent repression of PGC1α promoter activity. SUMOylation-resistant mutants of PARIS failed to repress PGC1α, suggesting a critical role for PARIS SUMOylation in hypertrophy. The present study, therefore, proposes a novel regulatory pathway where DJ-1 acts as an oxidative stress sensor and contributes to the feedback loop governing PARIS-mediated mitochondrial function. Copyright © 2020 American Society for Microbiology.

Citation

Dibyanti Mukherjee, Vivek Chander, Arun Bandyopadhyay. PARIS-DJ-1 Interaction Regulates Mitochondrial Functions in Cardiomyocytes, Which Is Critically Important in Cardiac Hypertrophy. Molecular and cellular biology. 2020 Dec 21;41(1)