Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

Lipoyl(Octanoyl) Transferase 2 (LIPT2) is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the...

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Main Authors:	Emanuele Bernardinelli, Roberta Costa, Giada Scantamburlo, Janet To, Rossana Morabito, Charity Nofziger, Carolina Doerrier, Gerhard Krumschnabel, Markus Paulmichl, Silvia Dossena
Format:	Article
Language:	English
Published:	Public Library of Science (PLoS) 2017-01-01
Series:	PLoS ONE
Online Access:	http://europepmc.org/articles/PMC5476274?pdf=render

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spelling	doaj-57e06cf59c9541d897b16deb103a63612020-11-24T20:45:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017959110.1371/journal.pone.0179591Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.Emanuele BernardinelliRoberta CostaGiada ScantamburloJanet ToRossana MorabitoCharity NofzigerCarolina DoerrierGerhard KrumschnabelMarkus PaulmichlSilvia DossenaLipoyl(Octanoyl) Transferase 2 (LIPT2) is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD) current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell), mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.http://europepmc.org/articles/PMC5476274?pdf=render
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Emanuele Bernardinelli Roberta Costa Giada Scantamburlo Janet To Rossana Morabito Charity Nofziger Carolina Doerrier Gerhard Krumschnabel Markus Paulmichl Silvia Dossena
spellingShingle	Emanuele Bernardinelli Roberta Costa Giada Scantamburlo Janet To Rossana Morabito Charity Nofziger Carolina Doerrier Gerhard Krumschnabel Markus Paulmichl Silvia Dossena Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death. PLoS ONE
author_facet	Emanuele Bernardinelli Roberta Costa Giada Scantamburlo Janet To Rossana Morabito Charity Nofziger Carolina Doerrier Gerhard Krumschnabel Markus Paulmichl Silvia Dossena
author_sort	Emanuele Bernardinelli
title	Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
title_short	Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
title_full	Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
title_fullStr	Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
title_full_unstemmed	Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
title_sort	mis-targeting of the mitochondrial protein lipt2 leads to apoptotic cell death.
publisher	Public Library of Science (PLoS)
series	PLoS ONE
issn	1932-6203
publishDate	2017-01-01
description	Lipoyl(Octanoyl) Transferase 2 (LIPT2) is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD) current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell), mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.
url	http://europepmc.org/articles/PMC5476274?pdf=render
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Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

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