S-Palmitoylation is a reversible lipid post-translational modification that has been observed on mitochondrial proteins, but both the regulation and functional consequences of mitochondrial S-palmitoylation are poorly understood. Here, we show that perturbing the 'erasers' of S-palmitoylation, acyl protein thioesterases (APTs), with either pan-active inhibitors or a mitochondrial-targeted APT inhibitor, diminishes the antioxidant buffering capacity of mitochondria. Surprisingly, this effect was not mediated by the only known mitochondrial APT, but rather by a resident mitochondrial protein with no known endogenous function, ABHD10. We show that ABHD10 is a member of the APT family of regulatory proteins and identify peroxiredoxin-5 (PRDX5), a key antioxidant protein, as a target of ABHD10 S-depalmitoylase activity. We then find that ABHD10 regulates the S-palmitoylation status of the nucleophilic active site residue of PRDX5, providing a direct mechanistic connection between ABHD10-mediated S-depalmitoylation of PRDX5 and its antioxidant capacity.

中文翻译：

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ABHD10 是一种 S-去棕榈酰化酶，通过 peroxiredoxin-5 影响氧化还原稳态。

S-棕榈酰化是一种可逆的脂质翻译后修饰，已在线粒体蛋白上观察到，但人们对线粒体 S-棕榈酰化的调节和功能后果知之甚少。在这里，我们表明用泛活性抑制剂或线粒体靶向 APT 抑制剂扰乱 S-棕榈酰化、酰基蛋白硫酯酶 (APT) 的“橡皮擦”会降低线粒体的抗氧化缓冲能力。令人惊讶的是，这种效应不是由唯一已知的线粒体 APT 介导，而是由一种没有已知内源功能的常驻线粒体蛋白 ABHD10 介导。我们表明 ABHD10 是 APT 调节蛋白家族的成员，并确定了关键的抗氧化蛋白 peroxiredoxin-5 (PRDX5) 作为 ABHD10 S-去棕榈酰酶活性的靶标。