The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.

Mitochondrial trifunctional protein (TFP) is a membrane-associated heterotetramer that catalyzes three of the four reactions needed to chain-shorten long-chain fatty acids inside the mitochondria. TFP is known to be heavily modified by acetyllysine and succinyllysine post-translational modifications...

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Autores principales:	Yuxun Zhang, Eric Goetzman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0fea4096b51e4042ac99449a7635439f
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spelling	oai:doaj.org-article:0fea4096b51e4042ac99449a7635439f2021-12-02T20:13:43ZThe enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.1932-620310.1371/journal.pone.0256619https://doaj.org/article/0fea4096b51e4042ac99449a7635439f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256619https://doaj.org/toc/1932-6203Mitochondrial trifunctional protein (TFP) is a membrane-associated heterotetramer that catalyzes three of the four reactions needed to chain-shorten long-chain fatty acids inside the mitochondria. TFP is known to be heavily modified by acetyllysine and succinyllysine post-translational modifications (PTMs), many of which are targeted for reversal by the mitochondrial sirtuin deacylases SIRT3 and SIRT5. However, the functional significance of these PTMs is not clear, with some reports showing TFP gain-of-function and some showing loss-of-function upon increased acylation. Here, we mapped the known SIRT3/SIRT5-targeted lysine residues onto the recently solved TFP crystal structure which revealed that many of the target sites are involved in substrate channeling within the TFPα subunit. To test the effects of acylation on substate channeling through TFPα, we enzymatically synthesized the physiological long-chain substrate (2E)-hexadecenoyl-CoA. Assaying TFP in SIRT3 and SIRT5 knockout mouse liver and heart mitochondria with (2E)-hexadecenoyl-CoA revealed no change in enzyme activity. Finally, we investigated the effects of lysine acylation on TFP membrane binding in vitro. Acylation did not alter recombinant TFP binding to cardiolipin-containing liposomes. However, the presence of liposomes strongly abrogated the acylation reaction between succinyl-CoA and TFP lysine residues. Thus, TFP in the membrane-bound state may be protected against lysine acylation.Yuxun ZhangEric GoetzmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0256619 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuxun Zhang Eric Goetzman The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
description	Mitochondrial trifunctional protein (TFP) is a membrane-associated heterotetramer that catalyzes three of the four reactions needed to chain-shorten long-chain fatty acids inside the mitochondria. TFP is known to be heavily modified by acetyllysine and succinyllysine post-translational modifications (PTMs), many of which are targeted for reversal by the mitochondrial sirtuin deacylases SIRT3 and SIRT5. However, the functional significance of these PTMs is not clear, with some reports showing TFP gain-of-function and some showing loss-of-function upon increased acylation. Here, we mapped the known SIRT3/SIRT5-targeted lysine residues onto the recently solved TFP crystal structure which revealed that many of the target sites are involved in substrate channeling within the TFPα subunit. To test the effects of acylation on substate channeling through TFPα, we enzymatically synthesized the physiological long-chain substrate (2E)-hexadecenoyl-CoA. Assaying TFP in SIRT3 and SIRT5 knockout mouse liver and heart mitochondria with (2E)-hexadecenoyl-CoA revealed no change in enzyme activity. Finally, we investigated the effects of lysine acylation on TFP membrane binding in vitro. Acylation did not alter recombinant TFP binding to cardiolipin-containing liposomes. However, the presence of liposomes strongly abrogated the acylation reaction between succinyl-CoA and TFP lysine residues. Thus, TFP in the membrane-bound state may be protected against lysine acylation.
format	article
author	Yuxun Zhang Eric Goetzman
author_facet	Yuxun Zhang Eric Goetzman
author_sort	Yuxun Zhang
title	The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
title_short	The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
title_full	The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
title_fullStr	The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
title_full_unstemmed	The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
title_sort	enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0fea4096b51e4042ac99449a7635439f
work_keys_str_mv	AT yuxunzhang theenzymeactivityofmitochondrialtrifunctionalproteinisnotalteredbylysineacetylationorlysinesuccinylation AT ericgoetzman theenzymeactivityofmitochondrialtrifunctionalproteinisnotalteredbylysineacetylationorlysinesuccinylation AT yuxunzhang enzymeactivityofmitochondrialtrifunctionalproteinisnotalteredbylysineacetylationorlysinesuccinylation AT ericgoetzman enzymeactivityofmitochondrialtrifunctionalproteinisnotalteredbylysineacetylationorlysinesuccinylation
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The enzyme activity of mitochondrial trifunctional protein is not altered by lysine acetylation or lysine succinylation.

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