期刊
AUTOPHAGY
卷 7, 期 9, 页码 935-956出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.7.9.15760
关键词
autophagosome; amphisome; PAS; phagophore; autolysosome; electron microscopy; morphology; ultrastructure; freeze-fracture; freeze-fixation; freeze-substitution; cytochemistry; immunoelectron microscopy; immunogold labeling; electron tomography
类别
资金
- Academy of Finland
- Sigrid Juselius Foundation
- Biocentrum Helsinki
- Magnus Ehrnrooth Foundation
- University of Helsinki
- Netherlands Organization for Health Research and Development [ZonMW-VIDI-917.76.329]
- Utrecht University
- Netherlands Organization for Scientific Research [700.59.003]
- Hungarian Scientific Research Funds OTKA [K75843, NK78012]
- Norwegian Cancer Society
- [21570069]
Autophagy was first discovered by transmission electron microscopy more than 50 years ago. For decades, electron microscopy was the only way to reliably detect autophagic compartments in cells because no specific protein markers were known. In the 1970s, however, the introduction of biochemical methods enabled quantitative studies of autophagic-lysosomal degradation, and in the 1980s specific biochemical assays for autophagic sequestration became available. Since the identification of autophagy-related genes in the 1990s, combined fluorescence microscopy, biochemical and genetic methods have taken the leading role in autophagy research. However, electron microscopy is still needed to confirm and verify results obtained by other methods, and also to produce novel knowledge that would not be achievable by any other experimental approach. Confocal microscopy, with its ever-improving resolution, is probably the best-suited morphological approach to investigate the dynamic aspects of autophagy. However, for analyzing the ultrastructural details of the many novel organelles and mechanisms involved in specific subtypes of autophagy, the electron microscope is still indispensable. This review will summarize the impact that electron microscopy has had on autophagy research since the discovery of this self-degradation process in the mid-1950s. Astonishingly, some of the novel concepts and principles of autophagy, presented in the recent studies, were already proposed several decades ago by the pioneering, accurate and passionate work of virtuoso electron microscopists.
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