High resolution respirometry in diagnostic of mitochondrial disorders caused by mitochondrial complex I deficiency
Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Le...
Saved in:
| Published in: | Biomeditsinskaia khimiia Vol. 63; no. 4; p. 327 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | Russian |
| Published: |
Russia (Federation)
01.07.2017
|
| Subjects: | |
| ISSN: | 2310-6972 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m.3308 T>G (n=2), m.3472 T>C (n=1) and 2 patients with earlier unknown substitutions m.3945 C>A and m.14441T>C. High-resolution respirometry (HRR) on the Oxygraph-2k instrument ("Oroboros corp.", Austria) was performed for complex analysis of the mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls. Flux control rations in intact cells R/E, (R-L)/E (p<0.05) were raised compared to the control. Rates of R, E, L normalized on the CS were statistically varied between patients and controls. In permeabilized fibroblasts we observed differences in CII/E, Rot/E, R/CII, CI/CII (p<0.05) between groups. These data highlight the dysfunction of the OXPHOS system and particularly CI. Increased citrate synthase level and decreased CI/CII ratio indicate compensatory metabolic response to respiratory chain dysfunction. Our results show applicability of HRR in revealing the biochemical abnormalities of complex I in fibroblasts of patients with LHON and Leigh-like syndrome. We also suggest HRR to be a useful method for inspection of other mutations causing complex I deficiency. |
|---|---|
| AbstractList | Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m.3308 T>G (n=2), m.3472 T>C (n=1) and 2 patients with earlier unknown substitutions m.3945 C>A and m.14441T>C. High-resolution respirometry (HRR) on the Oxygraph-2k instrument ("Oroboros corp.", Austria) was performed for complex analysis of the mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls. Flux control rations in intact cells R/E, (R-L)/E (p<0.05) were raised compared to the control. Rates of R, E, L normalized on the CS were statistically varied between patients and controls. In permeabilized fibroblasts we observed differences in CII/E, Rot/E, R/CII, CI/CII (p<0.05) between groups. These data highlight the dysfunction of the OXPHOS system and particularly CI. Increased citrate synthase level and decreased CI/CII ratio indicate compensatory metabolic response to respiratory chain dysfunction. Our results show applicability of HRR in revealing the biochemical abnormalities of complex I in fibroblasts of patients with LHON and Leigh-like syndrome. We also suggest HRR to be a useful method for inspection of other mutations causing complex I deficiency. Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m.3308 T>G (n=2), m.3472 T>C (n=1) and 2 patients with earlier unknown substitutions m.3945 C>A and m.14441T>C. High-resolution respirometry (HRR) on the Oxygraph-2k instrument ("Oroboros corp.", Austria) was performed for complex analysis of the mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls. Flux control rations in intact cells R/E, (R-L)/E (p<0.05) were raised compared to the control. Rates of R, E, L normalized on the CS were statistically varied between patients and controls. In permeabilized fibroblasts we observed differences in CII/E, Rot/E, R/CII, CI/CII (p<0.05) between groups. These data highlight the dysfunction of the OXPHOS system and particularly CI. Increased citrate synthase level and decreased CI/CII ratio indicate compensatory metabolic response to respiratory chain dysfunction. Our results show applicability of HRR in revealing the biochemical abnormalities of complex I in fibroblasts of patients with LHON and Leigh-like syndrome. We also suggest HRR to be a useful method for inspection of other mutations causing complex I deficiency.Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m.3308 T>G (n=2), m.3472 T>C (n=1) and 2 patients with earlier unknown substitutions m.3945 C>A and m.14441T>C. High-resolution respirometry (HRR) on the Oxygraph-2k instrument ("Oroboros corp.", Austria) was performed for complex analysis of the mitochondrial respiratory function in intact and permeabilized fibroblasts of patients and healthy controls. Flux control rations in intact cells R/E, (R-L)/E (p<0.05) were raised compared to the control. Rates of R, E, L normalized on the CS were statistically varied between patients and controls. In permeabilized fibroblasts we observed differences in CII/E, Rot/E, R/CII, CI/CII (p<0.05) between groups. These data highlight the dysfunction of the OXPHOS system and particularly CI. Increased citrate synthase level and decreased CI/CII ratio indicate compensatory metabolic response to respiratory chain dysfunction. Our results show applicability of HRR in revealing the biochemical abnormalities of complex I in fibroblasts of patients with LHON and Leigh-like syndrome. We also suggest HRR to be a useful method for inspection of other mutations causing complex I deficiency. |
| Author | Mikhaylova, S V Zakharova, E Yu Sheremet, N L Tsygankova, P G Krylova, T D Nevinitsyna, T A Itkis, Yu S |
| Author_xml | – sequence: 1 givenname: T D surname: Krylova fullname: Krylova, T D organization: Research Centre for Medical Genetics, Moscow, Russia – sequence: 2 givenname: P G surname: Tsygankova fullname: Tsygankova, P G organization: Research Centre for Medical Genetics, Moscow, Russia – sequence: 3 givenname: Yu S surname: Itkis fullname: Itkis, Yu S organization: Research Centre for Medical Genetics, Moscow, Russia – sequence: 4 givenname: N L surname: Sheremet fullname: Sheremet, N L organization: Research Institute of Eye Diseases, Moscow, Russia – sequence: 5 givenname: T A surname: Nevinitsyna fullname: Nevinitsyna, T A organization: Research Institute of Eye Diseases, Moscow, Russia – sequence: 6 givenname: S V surname: Mikhaylova fullname: Mikhaylova, S V organization: Russian Children's Clinical Hospital, Moscow, Russia – sequence: 7 givenname: E Yu surname: Zakharova fullname: Zakharova, E Yu organization: Research Centre for Medical Genetics, Moscow, Russia |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28862604$$D View this record in MEDLINE/PubMed |
| BookMark | eNpdkDtPwzAAhD0U0VK6MyGPLAG_HY9QAa1UBAPMkWM7raXEDnYikX9PEWVhupPu00l3F2AWYnAAXGF0i0uk5N3bw8uaICwFRYwSOQMLQjEqhJJkDlY5-xoRhhVnpToHc1KWggjEFiBt_P4Ak8uxHQcfw4_tfYqdG9IEfYDW632IefAGxgZ2fojmEINNXrfHLMdkXcrQ6DE7C-vpH2Fi17fuC26hdY033gUzXYKzRrfZrU66BB9Pj-_rTbF7fd6u73eFIcdFBadakppww0WtDTKo0Q2RxjprheG0rJlynCljkdK4tJIxTrDmAlMppMCKLMHNb2-f4ufo8lB1PhvXtjq4OOYKKyowV5LLI3p9Qse6c7bqk-90mqq_n8g3-95tOw |
| ContentType | Journal Article |
| DBID | NPM 7X8 |
| DOI | 10.18097/PBMC20176304327 |
| DatabaseName | PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| DocumentTitleAlternate | Respirometriia vysokogo razresheniia v diagnostike mitokhondrial'nykh zabolevaniĭ s narusheniem raboty I kompleksa dykhatel'noĭ tsepi mitokhondriĭ |
| ExternalDocumentID | 28862604 |
| Genre | English Abstract Journal Article |
| GroupedDBID | 53G NPM 7X8 |
| ID | FETCH-LOGICAL-c2097-53a72b25c56bac0c0faf27cdedd6c538b49e549cd09a18d744521a56137676192 |
| IEDL.DBID | 7X8 |
| ISSN | 2310-6972 |
| IngestDate | Thu Jul 10 23:51:55 EDT 2025 Wed Feb 19 02:33:58 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Keywords | high-resolution respirometry LHON Leigh syndrome complex I deficiency |
| Language | Russian |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c2097-53a72b25c56bac0c0faf27cdedd6c538b49e549cd09a18d744521a56137676192 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://pbmc.ibmc.msk.ru/pdf/PBMC-2017-63-4-327 |
| PMID | 28862604 |
| PQID | 1936159757 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1936159757 pubmed_primary_28862604 |
| PublicationCentury | 2000 |
| PublicationDate | 2017-Jul |
| PublicationDateYYYYMMDD | 2017-07-01 |
| PublicationDate_xml | – month: 07 year: 2017 text: 2017-Jul |
| PublicationDecade | 2010 |
| PublicationPlace | Russia (Federation) |
| PublicationPlace_xml | – name: Russia (Federation) |
| PublicationTitle | Biomeditsinskaia khimiia |
| PublicationTitleAlternate | Biomed Khim |
| PublicationYear | 2017 |
| SSID | ssib024195489 ssib040281610 ssib025541122 |
| Score | 2.023515 |
| Snippet | Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 327 |
| Title | High resolution respirometry in diagnostic of mitochondrial disorders caused by mitochondrial complex I deficiency |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/28862604 https://www.proquest.com/docview/1936159757 |
| Volume | 63 |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV07T8MwELaAMrDwEK_ykpFYI1rXjp0JQUUFQ6sOIHWLYp8jdSApSYvov-cuSYuEhITEkmSwh9jnu-_sz98xdmMlkQclIHLrpoFUvSgw4G0AXS-tEZHQqamKTejRyEwm0bjZcCsbWuXKJ1aOGnJHe-S3CDQw-EZa6bvZe0BVo-h0tSmhsclaPYQyROnSk7U9YXAiObN1uEb0LBFerMM5pk4GAU-nqj-H7iiMtGhOMg0JO44fhn2Mj7gCSbdO_45Bq1g02PvvX-yz3QaF8vvabA7YRrE4ZAVxPjim34010udsSnIG82LJpxmHmpaHfXie8jf0Beg7MyAT5tCoeJbcJYvSA7fLHy0q8rr_5M8cPMlW0J3PI_Y6eHzpPwVNSYbACRySQPUSLaxQToU2cR3XSZNUaAceIHToO62MPGacDjpR0jWgpUR4kFCSokPaMBHHbCvLM39Kl8XpeoryVlsjFb4VAOaC1qWhCZ2HNrteDWGMJk_nGEnm80UZfw9im53U8xDPam2OWJgqRZNnf-h9znZoemvy7QVrpbjg_SXbdh_zaVlcVbaEz9F4-AXzc9JS |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=High+resolution+respirometry+in+diagnostic+of+mitochondrial+disorders+caused+by+mitochondrial+complex+I+deficiency&rft.jtitle=Biomeditsinskaia+khimiia&rft.au=Krylova%2C+T+D&rft.au=Tsygankova%2C+P+G&rft.au=Itkis%2C+Yu+S&rft.au=Sheremet%2C+N+L&rft.date=2017-07-01&rft.issn=2310-6972&rft.volume=63&rft.issue=4&rft.spage=327&rft_id=info:doi/10.18097%2FPBMC20176304327&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2310-6972&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2310-6972&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2310-6972&client=summon |