Comment on "mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC".
Comment on "mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC".
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DOI：
10.1080/15548627.2021.1907269
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发表时间：
2021-12
期刊：
影响因子：
13.3
通讯作者：
McWilliams TG
中科院分区：
文献类型：
--
作者：
Ganley IG;Whitworth AJ;McWilliams TG
选择性自噬的一个方面是线粒体自噬(有丝分裂吞噬)，特别是PINK1-PRKN介导的有丝分裂吞噬，因为这直接与帕金森病有关。然而，在这种情况下，对不同的有丝分裂记者的初步研究已经导致了对结果/结果和结论的明显冲突。刘等人最近的一篇文章。试图通过并列比较两个吞丝分裂的报告系统mt-keima和mito-qc来调和这些不一致的发现[1]。当然，在Liu等人使用的基于细胞的分析中，对报告系统的直接比较是必要的。这涉及到PRKN的过度表达和流式细胞术，令人鼓舞的是，mt-keima产生了一个强有力的信号。然而，标题声称，mito-QC对于监测PINK1-PRKN依赖的有丝分裂吞噬不够敏感，应该平衡。作为一系列实验的一部分，MITO-QC已被独立研究小组用于多项发表的研究，以明确和可靠地显示有丝分裂吞噬增加，无论存在或不存在PINK1-PRKN，以及在内源性或过度表达的PRKN条件下。鼓励读者检查许多已发表的、控制良好和有效的研究中的一些[2-22]。此外，Liu et al.重复了他们自己的结果，证明了精疲力竭的运动诱导了mt-keima小鼠心脏中依赖PINK1的有丝分裂。这是非常令人鼓舞的，因为与这种类型的详尽运动研究相关的重复性很难。然而，我们想指出，Mito-QC和Mt-Keima之间的比较应该谨慎，有点类似于将苹果与橙子进行比较。一个令人信服的原因是，这些模型是使用不同的小鼠品系(Mt-Keima[12，23]的C57BL/6 j-NTAC与FVB/NJ)生成和维护的。与C57品系相比，FVB小鼠天生过度活跃，有昼夜节律失调和行为缺陷[24-26]，表现出神经解剖异常[27]，视网膜神经变性和失明[28]。值得注意的是，FVB和C57品系在适应和携带跑步机运动范例方面也存在显著差异[29]，包括肌肉组织中的线粒体差异[30]和不同的心脏生理[31]。我们想请读者参考Enriquez的文章，这篇文章强调了考虑遗传背景的重要性，以便有意义地比较数据[32]。最后，我们想解决刘等人的概念。McWilliams等人，2018年和Lee等人，2018年在PINK1-PRKN有丝分裂途径方面引起了争议[7，13]。从我们的角度来看，存在多条吞丝分裂途径是没有争议的。这些论文的主要结论是，在基础条件下，PINK1-PRKN通路不调节有丝分裂。这与刘等人的观察结果完全相同。在他们目前的研究中证实：在没有力竭运动的情况下，mt-keima小鼠心脏组织中的有丝分裂水平保持不变，无论是否有PINK1；即它们的基础有丝分裂水平独立于PINK1。我们还想重点介绍来自Goessling实验室的工作，该实验室最近生成了吞丝分裂的斑马鱼模型，并比较了基于Keima和Tandem mCherry-GFP的记者[33]。在这里，作者指出，两位记者都忠实地监测了有丝分裂吞噬，此外，特征的有丝分裂吞噬被确定为独立于PINK1和PRKN，而不是需要BNIP3。因此，考虑到独立实验室的多份出版物，使用…
One aspect of selective autophagy that has garnered intense interest is mitochondrial autophagy (mitophagy), particularly PINK1-PRKN-mediated mitophagy as this has direct implications for Parkinson disease. However, initial studies of different mitophagy reporters in this context have resulted in a perceived conflict of results/outcomes and conclusions. A recent article by Liu et al. attempts to reconcile these discordant findings by comparing side-by-side two mitophagy reporter systems, mt-Keima and mito-QC [1]. A direct comparison of the reporter systems is certainly warranted, and in the cell-based analyses used in Liu et al. that involve PRKN overexpression and flow cytometry, it is encouraging to see that mt-Keima produces a robust signal. However, the headline claim that mito-QC is insufficiently sensitive for monitoring PINK1-PRKN-dependent mitophagy should be brought into balance. mito-QC has been used in multiple published studies by independent groups as part of a series of experiments to clearly and reliably show increased mitophagy, either in the presence or absence of PINK1-PRKN, and under endogenous or overexpressed PRKN conditions. Readers are encouraged to examine some of the many published, well controlled and validated studies [2–22]. Additionally, Liu et al. repeated their own results demonstrating that exhaustive exercise induces PINK1-dependent mitophagy in the heart of mt-Keima mice. This is very encouraging given the difficult reproducibility associated with this type of exhaustive exercise study. However, we would like to point out that comparisons between mito-QC and mt-Keima should be made cautiously and are somewhat akin to comparing apples to oranges. One compelling reason is because the models have been generated and maintained using different mouse strains (C57BL/6 j-ntac versus FVB/NJ for mt-Keima [12, 23]). Compared to C57 lines, FVB mice are naturally hyperactive with circadian dysregulation and behavioral defects [24–26], display neuroanatomical abnormalities [27], retinal neurodegeneration and blindness [28]. It is important to note that significant differences also exist between FVB and C57 lines in adapting to and entrainment for treadmill exercise paradigms [29], including mitochondrial differences in muscle tissues [30] and divergent cardiac physiology [31]. We would like to refer the reader to the article by Enriquez that highlights the importance of considering genetic backgrounds in order to meaningfully compare data [32].Finally, we would like to address the notion by Liu et al. that McWilliams et al., 2018 and Lee et al., 2018 have generated controversy in terms of the PINK1-PRKN mitophagy pathway [7, 13]. From our perspective there is no controversy that multiple mitophagy pathways exist. The main conclusion of these papers was that the PINK1-PRKN pathway did not regulate mitophagy under basal conditions. This is the exact same observation that Liu et al. demonstrate in their current study: in the absence of exhaustive exercise, mitophagy levels in heart tissues of mt-Keima mice remain constant regardless of the presence or absence of PINK1; ie, their basal level of mitophagy is independent of PINK1. We would also like to highlight work from the Goessling Lab that recently generated zebrafish models of mitophagy and compared Keima-and tandem mCherry-GFP-based reporters [33]. Here, the authors noted that both reporters faithfully monitored mitophagy and, additionally, the characterized mitophagy was determined to be independent of PINK1 and PRKN, instead requiring BNIP3. Thus, taking into account multiple publications from independent laboratories, using …
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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DOI：
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发表时间：
2016-08-01
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Ganley IG