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- EMDB-75949: In situ cryo-ET analysis of mitochondria and autophagosome contac... -

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Basic information

Entry
Database: EMDB / ID: EMD-75949
TitleIn situ cryo-ET analysis of mitochondria and autophagosome contact in tauP301S Tg mouse cortical neurons Supplementary 2
Map dataMito-AV contact at 19500
Sample
  • Cell: Cortical neuron
Keywordsautophagosome-mitochondria contact / autophagy / mitochondrial bioenergetics / retrograde transport / tauopathy / UNKNOWN FUNCTION
Biological speciesMus musculus (house mouse)
Methodelectron tomography / cryo EM
AuthorsGonzalez CU / Jaber N
Funding support United States, 2 items
OrganizationGrant numberCountry
National Science Foundation (NSF, United States)MCB-2046180 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)R01NS089737 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Dysregulation of autophagosome-mitochondria contacts contributes to autophagy dysfunction and neurodegeneration in tauopathy.
Authors: Nuo Jia / Hongyuan Guan / Yantao Zuo / Yu Young Jeong / Niharika Amireddy / Gavesh Rajapaksha / Cuauhtemoc Ulises Gonzalez / Nora Jaber / Yun-Kyung Lee / Marialaina Nissenbaum / David J ...Authors: Nuo Jia / Hongyuan Guan / Yantao Zuo / Yu Young Jeong / Niharika Amireddy / Gavesh Rajapaksha / Cuauhtemoc Ulises Gonzalez / Nora Jaber / Yun-Kyung Lee / Marialaina Nissenbaum / David J Margolis / Wei Dai / Alexander W Kusnecov / Qian Cai /
Abstract: Mitochondria (Mito) engage in extensive communication with other organelles through membrane contacts. Perturbed mitochondria-organelle interactions are indicated in a variety of neurodegenerative ...Mitochondria (Mito) engage in extensive communication with other organelles through membrane contacts. Perturbed mitochondria-organelle interactions are indicated in a variety of neurodegenerative diseases, but the underlying mechanisms remain poorly understood. Here, we report a class of mitochondria-organelle communication: autophagosome/autophagic vacuole (AV)-Mito contact, which exhibits hypertethering in tauopathy neurons, consequently hampering AV retrograde transport. Such defects are attributed to accelerated turnover of the contact release factor TBC1D15, triggered by mitochondrial bioenergetic deficit-induced hyperactivity of the adenosine monophosphate-activated protein kinase (AMPK). Increasing TBC1D15 levels or repressing AMPK activity normalizes AV-Mito contact release and restores retrograde transport of AVs, thereby increasing autophagic cargo clearance and reducing tau burden in tauopathy axons. Furthermore, overexpression of TBC1D15 enhances autophagic clearance and attenuates tau pathology, alleviating neurodegeneration and cognitive dysfunction in tauopathy mice. Taken together, our study provides mechanistic insights into AV-Mito contact dysregulation in tauopathy-related autophagy failure, laying the groundwork for the development of potential therapeutics to combat tauopathy diseases.
History
DepositionMar 10, 2026-
Header (metadata) releaseJun 24, 2026-
Map releaseJun 24, 2026-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_75949.png

Downloads & links

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Map

FileDownload / File: emd_75949.map.gz / Format: CCP4 / Size: 1.1 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMito-AV contact at 19500
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
18.39 Å/pix.
x 201 pix.
= 3696.39 Å		18.39 Å/pix.
x 1440 pix.
= 26481.6 Å		18.39 Å/pix.
x 1024 pix.
= 18831.359 Å

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 18.39 Å
Density

Histogram

Histogram (log scale)
Minimum - Maximum-24.685124999999999 - 18.409147000000001
Average (Standard dev.)-0.000000007992408 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin208-20890
Dimensions14401024201
Spacing10241440201
CellA: 18831.36 Å / B: 26481.6 Å / C: 3696.39 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Cortical neuron

EntireName: Cortical neuron
Components
  • Cell: Cortical neuron

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Supramolecule #1: Cortical neuron

SupramoleculeName: Cortical neuron / type: cell / ID: 1 / Parent: 0
Source (natural)Organism: Mus musculus (house mouse)

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Experimental details

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Structure determination

Methodcryo EM
Processingelectron tomography
Aggregation statecell

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Sample preparation

BufferpH: 7.4
GridModel: Quantifoil R2/2 / Material: GOLD / Mesh: 300 / Support film - Material: SILICON DIOXIDE / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 293 K / Instrument: LEICA EM GP
SectioningOther: NO SECTIONING

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 4.32 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 8.0 µm / Nominal defocus min: 4.0 µm / Nominal magnification: 19500
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionSoftware - Name: IMOD (ver. 4.9.12) / Number images used: 37
CTF correctionType: NONE

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