A negative regulator of mitochondrial complex I assembly adapts respiration to cellular energy demand.

TMEM141 acts as a negative regulator of mitochondrial complex I assembly, with its loss boosting respiration and complex formation, especially under energy-demanding conditions.

• Why it matters: Understanding how mitochondrial respiration adapts to cellular energy needs is crucial for insights into metabolic regulation and related diseases, yet this process remains poorly understood.
• What they did: The study examined mammalian cells switching from glucose to galactose, revealing that TMEM141 interacts with the complex I assembly factor TIMMDC1 and is degraded by mitochondrial proteases, affecting complex I assembly.
• The result: Loss of TMEM141 enhances mitochondrial respiration and complex I assembly, but also increases oxidative damage and activates immune pathways, highlighting its role in balancing energy production and cellular health.