N-acetylcysteine modulates rotenone-induced mitochondrial Complex I dysfunction in THP-1 cells

Area of Science:

• Mitochondrial biology and pathophysiology
• Cellular response to oxidative stress

Background:

• Mitochondrial Complex I dysfunction and oxidative stress are implicated in various diseases, including neurodegenerative and metabolic disorders.
• Understanding cellular adaptation to Complex I dysfunction is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the effects of rotenone-induced mitochondrial dysfunction in THP-1 cells.
• To explore the protective potential of N-acetylcysteine (NAC) against rotenone-induced mitochondrial damage.

Main Methods:

• THP-1 cells were treated with low-dose rotenone to mimic peripheral mitochondrial dysfunction.
• The effects of N-acetylcysteine (NAC) pre-treatment on rotenone-induced changes were assessed.
• Key markers including mitochondrial superoxide, cell-free mitochondrial DNA, and specific Complex I subunit levels (NDUFS7, NDUFV1) were analyzed.

Main Results:

• Rotenone exposure increased mitochondrial superoxide, cell-free mitochondrial DNA, and NDUFS7 protein levels.
• NAC pre-treatment reduced cell-free mitochondrial DNA and NDUFS7 levels but did not affect mitochondrial superoxide.
• Rotenone induced NDUFV1 glutathionylation without altering NDUFV1 protein levels.

Conclusions:

• NAC demonstrates a protective effect against rotenone-induced mitochondrial dysfunction in THP-1 cells.
• NAC may mitigate Complex I alterations and preserve mitochondrial function by reducing cell-free mitochondrial DNA and stabilizing NDUFS7.
• Further research is warranted to elucidate NAC's precise mechanisms and therapeutic potential in conditions involving Complex I dysfunction.