Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease
Abstract Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondr...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07389-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544343310041088 |
|---|---|
| author | Julie Faitg Tracey Davey Ross Laws Conor Lawless Helen Tuppen Eric Fitton Doug Turnbull Amy E. Vincent |
| author_facet | Julie Faitg Tracey Davey Ross Laws Conor Lawless Helen Tuppen Eric Fitton Doug Turnbull Amy E. Vincent |
| author_sort | Julie Faitg |
| collection | DOAJ |
| description | Abstract Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondrial morphology evaluation at high magnification, even fewer that do so in situ and none in human muscle biopsies. Therefore, we have developed a method which combines functional assessment of mitochondria through Cytochrome c Oxidase (COX) histochemistry, with a 3D electron microscopy (EM) technique, serial block-face scanning electron microscopy (SBFSEM). Here we apply COX-SBFSEM to muscle samples from patients with single, large-scale mtDNA deletions, a cause of mitochondrial disease. These deletions cause oxidative phosphorylation deficiency, which can be observed through changes in COX activity. One of the main advantages of combining 3D-EM with the COX reaction is the ability to look at how per-mitochondrion oxidative phosphorylation status is spatially distributed within muscle fibres. Here we show a robust spatial pattern in COX-positive and intermediate-fibres and that the spatial pattern is less clear in COX-deficient fibres. |
| format | Article |
| id | doaj-art-2906f7cbdb4c401096147aabd4ae6a1e |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-2906f7cbdb4c401096147aabd4ae6a1e2025-01-12T12:35:43ZengNature PortfolioCommunications Biology2399-36422025-01-018111510.1038/s42003-024-07389-7Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial diseaseJulie Faitg0Tracey Davey1Ross Laws2Conor Lawless3Helen Tuppen4Eric Fitton5Doug Turnbull6Amy E. Vincent7Wellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityElectron Microscopy Research Services, Newcastle UniversityElectron Microscopy Research Services, Newcastle UniversityWellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityWellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityWellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityWellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityWellcome Centre for Mitochondrial Research, Translational and Clinical Research, Faculty of Medical Sciences, Newcastle UniversityAbstract Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondrial morphology evaluation at high magnification, even fewer that do so in situ and none in human muscle biopsies. Therefore, we have developed a method which combines functional assessment of mitochondria through Cytochrome c Oxidase (COX) histochemistry, with a 3D electron microscopy (EM) technique, serial block-face scanning electron microscopy (SBFSEM). Here we apply COX-SBFSEM to muscle samples from patients with single, large-scale mtDNA deletions, a cause of mitochondrial disease. These deletions cause oxidative phosphorylation deficiency, which can be observed through changes in COX activity. One of the main advantages of combining 3D-EM with the COX reaction is the ability to look at how per-mitochondrion oxidative phosphorylation status is spatially distributed within muscle fibres. Here we show a robust spatial pattern in COX-positive and intermediate-fibres and that the spatial pattern is less clear in COX-deficient fibres.https://doi.org/10.1038/s42003-024-07389-7 |
| spellingShingle | Julie Faitg Tracey Davey Ross Laws Conor Lawless Helen Tuppen Eric Fitton Doug Turnbull Amy E. Vincent Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease Communications Biology |
| title | Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease |
| title_full | Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease |
| title_fullStr | Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease |
| title_full_unstemmed | Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease |
| title_short | Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease |
| title_sort | mapping mitochondrial morphology and function cox sbfsem reveals patterns in mitochondrial disease |
| url | https://doi.org/10.1038/s42003-024-07389-7 |
| work_keys_str_mv | AT juliefaitg mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT traceydavey mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT rosslaws mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT conorlawless mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT helentuppen mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT ericfitton mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT dougturnbull mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease AT amyevincent mappingmitochondrialmorphologyandfunctioncoxsbfsemrevealspatternsinmitochondrialdisease |