Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Internal Medicine, Division of Nephrology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Biomolecules. 2020 Apr 10;10(4):585. doi: 10.3390/biom10040585.
Voltage-dependent anion channels (VDACs) constitute major transporters mediating bidirectional movement of solutes between cytoplasm and mitochondria. We aimed to determine if VDAC1 plays a role in recovery of mitochondrial and kidney functions after ischemia-induced acute kidney injury (AKI). Kidney function decreased after ischemia and recovered in wild-type (WT), but not in VDAC1-deficient mice. Mitochondrial maximum respiration, activities of respiratory complexes and FF-ATPase, and ATP content in renal cortex decreased after ischemia and recovered in WT mice. VDAC1 deletion reduced respiration and ATP content in non-injured kidneys. Further, VDAC1 deletion blocked return of activities of respiratory complexes and FF-ATPase, and recovery of respiration and ATP content after ischemia. Deletion of VDAC1 exacerbated ischemia-induced mitochondrial fission, but did not aggravate morphological damage to proximal tubules after ischemia. However, VDAC1 deficiency impaired recovery of kidney morphology and increased renal interstitial collagen accumulation. Thus, our data show a novel role for VDAC1 in regulating renal mitochondrial dynamics and recovery of mitochondrial function and ATP levels after AKI. We conclude that the presence of VDAC1 (1) stimulates capacity of renal mitochondria for respiration and ATP production, (2) reduces mitochondrial fission, (3) promotes recovery of mitochondrial function and dynamics, renal morphology, and kidney functions, and (4) increases survival after AKI.
电压依赖性阴离子通道（VDACs）构成了介导细胞质和线粒体之间溶质双向运动的主要转运体。我们旨在确定 VDAC1 是否在缺血性急性肾损伤（AKI）后线粒体和肾脏功能的恢复中发挥作用。缺血后肾脏功能下降，在野生型（WT）小鼠中恢复，但在 VDAC1 缺陷型小鼠中则不能恢复。缺血后肾脏皮质中线粒体最大呼吸、呼吸复合物和 FF-ATP 酶的活性以及 ATP 含量下降，而在 WT 小鼠中恢复。VDAC1 缺失减少了未受损肾脏的呼吸和 ATP 含量。此外，VDAC1 缺失阻断了呼吸复合物和 FF-ATP 酶活性以及缺血后呼吸和 ATP 含量的恢复。VDAC1 的缺失加剧了缺血诱导的线粒体裂变，但在缺血后并未加重近端肾小管的形态损伤。然而，VDAC1 缺陷损害了肾脏形态的恢复，并增加了肾间质胶原的积累。因此，我们的数据显示 VDAC1 在调节肾脏线粒体动力学和 AKI 后线粒体功能和 ATP 水平的恢复中具有新的作用。我们得出结论，VDAC1 的存在（1）刺激了肾脏线粒体的呼吸和 ATP 产生能力，（2）减少了线粒体裂变，（3）促进了线粒体功能和动力学、肾脏形态和肾脏功能的恢复，以及（4）增加了 AKI 后的存活率。
