Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults
Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial–iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle bio...
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MDPI AG
2020-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/12/2579 |
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| author | Anna Picca Sunil K. Saini Robert T. Mankowski George Kamenov Stephen D. Anton Todd M. Manini Thomas W. Buford Stephanie E. Wohlgemuth Rui Xiao Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei David A. Hood Emanuele Marzetti Christiaan Leeuwenburgh |
| author_facet | Anna Picca Sunil K. Saini Robert T. Mankowski George Kamenov Stephen D. Anton Todd M. Manini Thomas W. Buford Stephanie E. Wohlgemuth Rui Xiao Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei David A. Hood Emanuele Marzetti Christiaan Leeuwenburgh |
| author_sort | Anna Picca |
| collection | DOAJ |
| description | Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial–iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA<sup>4977</sup>) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (<sup>56</sup>Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA<sup>4977</sup> relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability. |
| first_indexed | 2024-03-10T14:23:47Z |
| format | Article |
| id | doaj.art-e40018526c4a45c79bad18799a9009e8 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:23:47Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e40018526c4a45c79bad18799a9009e82023-11-20T23:12:03ZengMDPI AGCells2073-44092020-12-01912257910.3390/cells9122579Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older AdultsAnna Picca0Sunil K. Saini1Robert T. Mankowski2George Kamenov3Stephen D. Anton4Todd M. Manini5Thomas W. Buford6Stephanie E. Wohlgemuth7Rui Xiao8Riccardo Calvani9Hélio José Coelho-Júnior10Francesco Landi11Roberto Bernabei12David A. Hood13Emanuele Marzetti14Christiaan Leeuwenburgh15Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyDepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USADepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USADepartment of Geological Sciences, University of Florida, Gainesville, FL 32605, USADepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USADepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USADepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USADepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USADepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USAFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyInstitute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyMuscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, CanadaFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, ItalyDepartment of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32611, USAMitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial–iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA<sup>4977</sup>) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (<sup>56</sup>Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA<sup>4977</sup> relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.https://www.mdpi.com/2073-4409/9/12/2579autophagyiron dyshomeostasisiron metabolismiron isotopesmitochondriamitochondrial quality control |
| spellingShingle | Anna Picca Sunil K. Saini Robert T. Mankowski George Kamenov Stephen D. Anton Todd M. Manini Thomas W. Buford Stephanie E. Wohlgemuth Rui Xiao Riccardo Calvani Hélio José Coelho-Júnior Francesco Landi Roberto Bernabei David A. Hood Emanuele Marzetti Christiaan Leeuwenburgh Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults Cells autophagy iron dyshomeostasis iron metabolism iron isotopes mitochondria mitochondrial quality control |
| title | Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults |
| title_full | Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults |
| title_fullStr | Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults |
| title_full_unstemmed | Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults |
| title_short | Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults |
| title_sort | altered expression of mitoferrin and frataxin larger labile iron pool and greater mitochondrial dna damage in the skeletal muscle of older adults |
| topic | autophagy iron dyshomeostasis iron metabolism iron isotopes mitochondria mitochondrial quality control |
| url | https://www.mdpi.com/2073-4409/9/12/2579 |
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