Quantification of cristae architecture reveals time-dependent characteristics of individual mitochondria

被引：32

作者：

Segawa, Mayuko ^{[1
,2
]}

Wolf, Dane M. ^{[1
,2
,3
]}

Hultgren, Nan W. ^{[4
]}

Williams, David S. ^{[4
]}

van der Bliek, Alexander M. ^{[5
,6
]}

Shackelford, David B. ^{[7
,8
]}

Liesa, Marc ^{[1
,2
]}

Shirihai, Orian S. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[3] Boston Univ, Grad Med Sci, Grad Program Nutr & Metab, Sch Med, Boston, MA 02118 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Dept Ophthalmol & Neurobiol, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA

[6] Univ Calif Los Angeles, Dept Biol Chem, David Geffen Sch Med, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pulm & Crit Care Med, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

来源：

LIFE SCIENCE ALLIANCE | 2020年 / 3卷 / 07期

关键词：

ATP SYNTHASE; MICROSCOPY; OPA1;

D O I：

10.26508/lsa.201900620

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recent breakthroughs in live-cell imaging have enabled visualization of cristae, making it feasible to investigate the structure-function relationship of cristae in real time. However, quantifying live-cell images of cristae in an unbiased way remains challenging. Here, we present a novel, semi-automated approach to quantify cristae, using the machine-learning Trainable Weka Segmentation tool. Compared with standard techniques, our approach not only avoids the bias associated with manual thresholding but more efficiently segments cristae from Airyscan and structured illumination microscopy images. Using a cardiolipin-deficient cell line, as well as FCCP, we show that our approach is sufficiently sensitive to detect perturbations in cristae density, size, and shape. This approach, moreover, reveals that cristae are not uniformly distributed within the mitochondrion, and sites of mitochondria) fission are localized to areas of decreased cristae density. After a fusion event, individual cristae from the two mitochondria, at the site of fusion, merge into one object with distinct architectural values. Overall, our study shows that machine learning represents a compelling new strategy for quantifying cristae in living cells.

引用

页数：14

共 32 条

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