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. 2017 Jan 5;8(1):e2531. doi: 10.1038/cddis.2016.443

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Copyright © 2017 The Author(s)

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Mitochondrial fragmentation and mitophagy in 26S proteasome-impaired neurons. (a) Representative EMs of control (i) and Psmc1^fl/fl;CaMKIIα-Cre (ii) cortical neurons at 6 weeks old. Enlarged views of mitochondria in boxed areas are shown in (iii, control) and (iv, Psmc1^fl/fl;CaMKIIα-Cre). n, nucleus; i, inclusion; m, mitochondria; v, vesicle. Scale 2 μm (i and ii) and 500 nm (iii and iv). (b and c) Smoothed line frequency histograms of mitochondrial aspect ratio and size distribution respectively for control and Psmc1^fl/fl;CaMKIIα-Cre neurons. P<0.001 (b) and P<0.0001 (c) by Mann–Whitney test. (d) Representative AVs in 6-week-old Psmc1^fl/fl;CaMKIIα-Cre cortical neurons (i–v) with heterogeneous intraluminal contents; vesicles (i; v), amorphous material (ii; asterisk) and condensed mitochondria (ii-v; m). Aggregates of condensed mitochondria resembling mitochondria undergoing autophagy are shown (iv and v; arrows). Representative primary (vi; pl) and secondary lysosomes (vii; sl) in 6-week-old control cortical neurons. Scale 200 nm. (e) Quantification of the total number of AVs and AVs containing mitochondria in 6-week-old control and Psmc1^fl/fl;CaMKIIα-Cre neurons. Error bars represent S.E.M. **P<0.01 and ***P<0.001 by unpaired Student's t-test. Quantification in Figure 1 used 18 randomly selected neurons from three different control and Psmc1^fl/fl;CaMKIIα-Cre brains