“…Several upregulated genes have been shown to restrain basal mitochondrial respiratory capacity with respective mechanisms other than mitophagy, including BNIP3 (Zhang et al, 2009;Rikka et al, 2011;Liu et al, 2017b), BNIP3L (Mughal et al, 2018;da Silva Rosa et al, 2020), HMOX1 (Zukor et al, 2009;Meyer et al, 2018), PDK4 (Oh et al, 2017;Ma et al, 2020), and MIR210 (microRNA-210) (Chan et al, 2009;Nakada et al, 2020; Table 1). The mitochondrial membrane potential ( ψm) normally remains stable for the respiratory chain to generate ATP and thus can be used as a fundamental indicator of mitochondrial function (Zorova et al, 2018;Li et al, 2020). We found that ψm was reduced after 24 h of FG-4592 treatment, which was further exacerbated after 48 h (Figures 4G,H), suggesting that mitochondrial function was compromised by activation of HIF and downstream factors before substantial mitophagy induction.…”