Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H, Abramov AY, Hardy J, Wood NW, Whitworth AJ, Laman H, Plun-Favreau H.
The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy.
Nat Neurosci. 2013 Sep;16(9):1257-65.
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The key thing these authors show in this paper, and this is why it is an important study, is that Fbxo7 mutations interact with an established pathway for recessive parkinsonism. The authors clearly show that the mutations are loss of function, which is probably predicted based on the genetics, but is very helpful to demonstrate. This is shown in patient samples, which is helpful, and I think it confirms that mitophagy is likely important in recessive forms of parkinsonism.
There are some things that still need to be resolved. As the authors themselves state, the rescue of parkin null phenotypes by over expression of Fbxo7 cannot be due to physical interaction between Fbxo7 and parkin, and they suggest another (unidentified) E3 ligase must be involved. I think it's also intriguing that Fbxo7 doesn't rescue loss of PINK1. These are fine grained mechanistic details, and don’t detract from the current paper, but I am intrigued to know the answer. This is of particular interest in relation to Drosophila, which to my best knowledge, has no endogenous Fbxo7 homologue. So how Fbxo7 rescues those animals is very interesting.
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