Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]

Publication Date:
2018-01-13
Publisher:
The American Society for Biochemistry and Molecular Biology (ASBMB)
Print ISSN:
0021-9258
Electronic ISSN:
1083-351X
Topics:
Biology
Chemistry and Pharmacology
Published by:
http://www.asbmb.org/
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autor E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
beschreibung Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), monolyso-CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I + III. Mechanistically, the reduction in enzymatic activities was not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid–protein binding, which has implications for the ongoing debate about
citation_standardnr 6138303
datenlieferant ipn_articles
feed_id 43
feed_publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
feed_publisher_url http://www.asbmb.org/
insertion_date 2018-01-13
journaleissn 1083-351X
journalissn 0021-9258
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Biochemistry and Molecular Biology (ASBMB)
quelle Journal of Biological Chemistry
relation http://feedproxy.google.com/~r/jbc/SUcv/~3/Zi74kmbrYbQ/466.short
search_space articles
shingle_author_1 E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
shingle_author_2 E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
shingle_author_3 E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
shingle_author_4 E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
shingle_catch_all_1 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), monolyso-CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I + III. Mechanistically, the reduction in enzymatic activities was not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid–protein binding, which has implications for the ongoing debate about
E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_2 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), monolyso-CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I + III. Mechanistically, the reduction in enzymatic activities was not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid–protein binding, which has implications for the ongoing debate about
E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_3 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), monolyso-CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I + III. Mechanistically, the reduction in enzymatic activities was not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid–protein binding, which has implications for the ongoing debate about
E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_catch_all_4 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), monolyso-CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I + III. Mechanistically, the reduction in enzymatic activities was not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid–protein binding, which has implications for the ongoing debate about
E. Madison Sullivan, Edward Ross Pennington, Genevieve C. Sparagna, Maria J. Torres, P. Darrell Neufer, Mitchel Harris, James Washington, Ethan J. Anderson, Tonya N. Zeczycki, David A. Brown, Saame Raza Shaikh
The American Society for Biochemistry and Molecular Biology (ASBMB)
0021-9258
00219258
1083-351X
1083351X
shingle_title_1 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
shingle_title_2 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
shingle_title_3 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
shingle_title_4 Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
timestamp 2025-06-30T23:32:01.487Z
titel Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
titel_suche Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome [Membrane Biology]
topic W
V
uid ipn_articles_6138303