Figure 3. Mitochondrial complex I is not necessary for PQ-induced cell death.

(a) Non-targeting control, clonal POR-null (POR_KO2), and clonal NDUFA6-null (NDUFA6_KO) Jurkat cells were treated with varying concentrations of PQ for 7 days and the percentage of cellular viability was assessed. For statistical analysis, the POR_KO2 cells were compared. (b) Live cell viability was determined following treatment with varying concentrations of mitochondrially targeted paraquat (MitoPQ) for 7 days in non-targeting control Jurkat cells as well as clonal POR-null, ATP7A-null, SLC45A4-null, and NDUFA6-null Jurkat cells. (c) Non-targeting (NT) control, POR-null, ATP7A-null, and SLC45A4-null Jurkat cells were treated with 150 μM PQ for 24 hours and PQ uptake into the cells was analyzed by high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS). Results are normalized to non-targeting control Jurkat cells. (d) SOD activity (U/mL) was measured in non-targeting (NT) control Jurkat cells as well as clonal POR-null, ATP7A-null, and SLC45A4-null Jurkat cells. (e) Structure of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ; 4). (f) Live cell viability was determined following treatment with varying concentrations of the redox cycler and pro–oxidant DMNQ for 7 days in non-targeting control, POR-null, ATP7A-null, and SLC45A4-null Jurkat cells. For a–d and f, error bars represent SEM (n=4 independent experiments for a,b,d,f; n=3 independent experiments for c). **, p < 0.01 compared to control cells.