Our experimental results showed that: (1) GNPAT and DRP1 proteins were highly expressed in COPD; (2) CSE and the mitochondrial fission inducer TA9 enhanced mitochondrial fission and dysfunction, and also promoted cell death; (3) GNPAT/USP30 increased the stability of the DRP1 protein, and thereby regulated mitochondrial fission and functional damage. Here, USP30 is linked to chronic obstructive pulmonary disease.