Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts
Background: Mitochondrial <inline-formula> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula>-oxidation of fatty acids is the primary energy source for the heart and carried out by Hydroxy Acyl-CoA Dehydrogenase (HADH) encoded trifunctional protein. Mu...
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| Format: | Article |
| Language: | English |
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IEEE
2021-01-01
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| Series: | IEEE Journal of Translational Engineering in Health and Medicine |
| Subjects: | |
| Online Access: | https://ieeexplore.ieee.org/document/9514507/ |
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| author | Farnaz H. Foomani Jason A. Jarzembowski Soudeh Mostaghimi Shima Mehrvar Suresh N. Kumar Mahsa Ranji |
| author_facet | Farnaz H. Foomani Jason A. Jarzembowski Soudeh Mostaghimi Shima Mehrvar Suresh N. Kumar Mahsa Ranji |
| author_sort | Farnaz H. Foomani |
| collection | DOAJ |
| description | Background: Mitochondrial <inline-formula> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula>-oxidation of fatty acids is the primary energy source for the heart and carried out by Hydroxy Acyl-CoA Dehydrogenase (HADH) encoded trifunctional protein. Mutations in the genes encoding mitochondrial proteins result in functionally defective protein complexes that contribute to energy deficiencies, excessive reactive oxygen species (ROS) production, and accumulation of damaged mitochondria. We hypothesize that a dramatic alternation in redox state and associated mitochondrial dysfunction is the underlying cause of Fatty Acid Oxidation (FAO) deficiency mutant, resulting in heart failure. Mitochondrial co-enzymes, NADH and FAD, are autofluorescent metabolic indices of cells when imaged, yield a quantitative assessment of the cells’ redox status and, in turn, that of the tissue and organ. Method: We utilized an optical cryo-imager to quantitively evaluate the three-dimensional distribution of mitochondrial redox state in newborn rats’ hearts and kidneys. Redox ratio (RR) assessment shows that mitochondrial dysfunction is extreme and could contribute to severe heart problems and eventual heart failure in the mutants. Results: Three-dimensional redox ratio (NADH/FAD) rendering, and the volumetric mean value calculations confirmed significantly decreased cardiac RR in mutants by 31.90% and 12.32%, in renal mitochondrial RR compared to wild-type control. Further, histological assessment of newborn heart myocardial tissue indicated no significant difference in myocardial tissue architecture in both control and severe (HADHA<sup>e4−/−</sup>) conditions. Conclusion: These results demonstrate that optical imaging can accurately estimate the redox state changes in newborn rat organs. It is also apparent that the FAO mutant’s heart tissue with a low redox ratio is probably more vulnerable to cumulative damages than kidneys and fails prematurely, contributing to sudden death. |
| first_indexed | 2024-12-21T16:49:10Z |
| format | Article |
| id | doaj.art-59ae9cfd806f4407af181bd7a78d517e |
| institution | Directory Open Access Journal |
| issn | 2168-2372 |
| language | English |
| last_indexed | 2024-12-21T16:49:10Z |
| publishDate | 2021-01-01 |
| publisher | IEEE |
| record_format | Article |
| series | IEEE Journal of Translational Engineering in Health and Medicine |
| spelling | doaj.art-59ae9cfd806f4407af181bd7a78d517e2022-12-21T18:56:55ZengIEEEIEEE Journal of Translational Engineering in Health and Medicine2168-23722021-01-0191710.1109/JTEHM.2021.31049669514507Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat HeartsFarnaz H. Foomani0https://orcid.org/0000-0003-3635-3564Jason A. Jarzembowski1Soudeh Mostaghimi2Shima Mehrvar3https://orcid.org/0000-0003-2563-7000Suresh N. Kumar4Mahsa Ranji5https://orcid.org/0000-0002-4185-5676Department of Electrical Engineering, Biophotonics Laboratory, University of Wisconsin–Milwaukee, Milwaukee, WI, USADepartment of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USADepartment of Electrical Engineering, Biophotonics Laboratory, University of Wisconsin–Milwaukee, Milwaukee, WI, USADepartment of Electrical Engineering, Biophotonics Laboratory, University of Wisconsin–Milwaukee, Milwaukee, WI, USADepartment of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USADepartment of Electrical Engineering and Computer Science (EECS), Biophotonics Laboratory, ISENSE Institute, Florida Atlantic University, Boca Raton, FL, USABackground: Mitochondrial <inline-formula> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula>-oxidation of fatty acids is the primary energy source for the heart and carried out by Hydroxy Acyl-CoA Dehydrogenase (HADH) encoded trifunctional protein. Mutations in the genes encoding mitochondrial proteins result in functionally defective protein complexes that contribute to energy deficiencies, excessive reactive oxygen species (ROS) production, and accumulation of damaged mitochondria. We hypothesize that a dramatic alternation in redox state and associated mitochondrial dysfunction is the underlying cause of Fatty Acid Oxidation (FAO) deficiency mutant, resulting in heart failure. Mitochondrial co-enzymes, NADH and FAD, are autofluorescent metabolic indices of cells when imaged, yield a quantitative assessment of the cells’ redox status and, in turn, that of the tissue and organ. Method: We utilized an optical cryo-imager to quantitively evaluate the three-dimensional distribution of mitochondrial redox state in newborn rats’ hearts and kidneys. Redox ratio (RR) assessment shows that mitochondrial dysfunction is extreme and could contribute to severe heart problems and eventual heart failure in the mutants. Results: Three-dimensional redox ratio (NADH/FAD) rendering, and the volumetric mean value calculations confirmed significantly decreased cardiac RR in mutants by 31.90% and 12.32%, in renal mitochondrial RR compared to wild-type control. Further, histological assessment of newborn heart myocardial tissue indicated no significant difference in myocardial tissue architecture in both control and severe (HADHA<sup>e4−/−</sup>) conditions. Conclusion: These results demonstrate that optical imaging can accurately estimate the redox state changes in newborn rat organs. It is also apparent that the FAO mutant’s heart tissue with a low redox ratio is probably more vulnerable to cumulative damages than kidneys and fails prematurely, contributing to sudden death.https://ieeexplore.ieee.org/document/9514507/Mitochondrial dysfunctionoptical imagingredox stateHADHnewborn rats |
| spellingShingle | Farnaz H. Foomani Jason A. Jarzembowski Soudeh Mostaghimi Shima Mehrvar Suresh N. Kumar Mahsa Ranji Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts IEEE Journal of Translational Engineering in Health and Medicine Mitochondrial dysfunction optical imaging redox state HADH newborn rats |
| title | Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts |
| title_full | Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts |
| title_fullStr | Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts |
| title_full_unstemmed | Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts |
| title_short | Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts |
| title_sort | optical metabolic imaging of mitochondrial dysfunction on hadh mutant newborn rat hearts |
| topic | Mitochondrial dysfunction optical imaging redox state HADH newborn rats |
| url | https://ieeexplore.ieee.org/document/9514507/ |
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