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Figure 1. Mice with acute deletion of p62 (p62icKO) are susceptible to hypoxia.
Figure 2. Cardiomyocyte p62 deletion impairs Hif-1α and Nrf2 target gene expression under normoxia and hypoxia.
Figure 3. Knockdown of p62 reduces Hif-1α stabilization and its transcriptional in cultured H9c2 rat cardiomyoblasts exposed to hypoxia.
Figure 4. Loss of p62 decreases and gain of p62 increases Nrf2 protein expression and transcriptional activity in cultured H9c2 cells.
Figure 5. Loss of p62 induces Nrf2 ubiquitination.
Figure 6. Nrf2 ubiquitination is mediated by Cullin 3 in H9c2 cells lacking p62.
Figure 7. Hypoxia upregulates and loss of p62 dampens Nrf2 protein levels.
Supplemental Figure 1. p62cKO hearts show mild cardiac contractile dysfunction and reduced Nrf2 signaling.
Supplemental Figure 2. Hypoxic stress decreases Nqo1 protein levels in p62icKO mice.
Supplemental Figure 3. Time-course of hypoxia in mice.
Supplemental Figure 4. Proteasome inhibition causes accumulation of Keap1 protein and loss of p62 does not alter Nrf2 or Keap1 gene expression.
Supplemental Figure 5. Loss of p62 decreases Nrf2 nuclear translocation.
Supplemental Figure 6. p62 depletion alters macroautophagy in H9c2 cardiomyocytes.
Supplemental Figure 7. p62 depletion heightens Nrf2-Keap1 colocalization.
Supplemental Figure 8. Loss of p62 accelerates Nrf2 protein degradation.
Supplemental Figure 9. p62 depletion heightens oxidative stress and decreases viability of H9c2 cells.

图1 急性敲除p62的小鼠（p62icKO）对缺氧易感。
图2 常氧及缺氧条件下，心肌细胞p62敲除会损害缺氧诱导因子-1α（Hif-1α）和核因子E2相关因子2（Nrf2）的靶基因表达。
图3 在暴露于缺氧环境的培养大鼠心肌母细胞H9c2中，p62敲低会减弱Hif-1α的稳定性及其转录活性。
图4 在培养的H9c2细胞中，p62缺失会降低Nrf2蛋白表达及转录活性，而p62过表达则会增强二者水平。
图5 p62缺失会诱导Nrf2发生泛素化。
图6 在缺失p62的H9c2细胞中，Nrf2的泛素化由Cullin 3介导。
图7 缺氧会上调Nrf2蛋白水平，而p62缺失则会抑制这一过程。
补充图1 p62条件性敲除（p62cKO）小鼠心脏表现为轻度心肌收缩功能障碍及Nrf2信号通路减弱。
补充图2 缺氧应激会降低p62icKO小鼠体内的Nqo1蛋白水平。
补充图3 小鼠缺氧处理的时间进程。
补充图4 蛋白酶体抑制会导致Keap1蛋白积累，而p62缺失不会改变Nrf2或Keap1的基因表达。
补充图5 p62缺失会减少Nrf2的核转位。
补充图6 p62敲低会改变H9c2心肌细胞的巨自噬过程。
补充图7 p62敲低会增强Nrf2与Keap1的共定位。
补充图8 p62缺失会加速Nrf2蛋白的降解。
补充图9 p62敲低会加剧氧化应激并降低H9c2细胞的存活率。