LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson disease

Autophagy
Charleen T ChuValerian E Kagan

Abstract

Mitophagy, or the selective clearance of mitochondria by autophagy, plays a key role in mitochondrial quality control. Due to their postmitotic nature and metabolic dependence on mitochondria, either insufficient or unchecked mitophagy is detrimental to neurons. To better understand signals that regulate this process, we treated primary rat cortical neurons with the electron transport chain complex I inhibitor rotenone to elicit mitophagy. The lipidomic profiles of mitochondria from control or injured neurons were analyzed by mass spectrometry, revealing a significant redistribution of cardiolipin (CL) from the inner mitochondrial membrane to the outer mitochondrial surface. Direct liposome-binding studies, computational modeling, and site-directed mutagenesis indicate that microtubule-associated protein 1 light chain 3 (MAP1LC3/LC3), a defining protein of autophagic membranes, binds to CL. Preventing this interaction inhibits rotenone-induced mitochondrial delivery to autophagosomes and lysosomes and attenuates mitochondrial loss as assessed by western blot. The CL-LC3 interaction is also important for mitophagy induced by other stimuli including 6-hydroxydopamine, another chemical model of Parkinson disease. Given that a cons...Continue Reading

Citations

May 31, 2014·Nature Cell Biology·Alexandra StolzIvan Dikic
Dec 15, 2015·Annals of the American Thoracic Society·Mauricio RojasOliver Eickelberg
Oct 4, 2015·Redox Biology·Joe Dan DunnThierry Soldati
Sep 30, 2015·Chemistry and Physics of Lipids·Gerard J Gaspard, Christopher R McMaster
Jun 24, 2014·Traffic·Yasushi TamuraToshiya Endo
Sep 24, 2015·Cellular and Molecular Life Sciences : CMLS·Sebastian Wesselborg, Björn Stork
Oct 7, 2015·Frontiers in Cell and Developmental Biology·Michael SchraderMarkus Islinger
Jan 18, 2015·Biochimica Et Biophysica Acta·Mohsin KhanAleem Siddiqui
Jan 31, 2015·Biochimica Et Biophysica Acta·Mohammed Dany, Besim Ogretmen
Aug 25, 2015·Biophysical Journal·Joan Planas-IglesiasJudith Klein-Seetharaman
Apr 14, 2016·Progress in Neurobiology·Chai K LimGilles J Guillemin
Sep 18, 2014·CNS Neuroscience & Therapeutics·Ruo-Yang ShiJi-Ming Kong
Jul 30, 2015·Mediators of Inflammation·Pierre LapaquetteMarie-Agnès Bringer
Aug 25, 2015·BioMed Research International·Zheni ShenMiriam L Greenberg
May 17, 2014·Molecular Neurobiology·Abhishek Kumar MishraMahendra Pratap Singh
Oct 9, 2014·Journal of Bioenergetics and Biomembranes·Tyler G Demarest, Margaret M McCarthy
Jul 6, 2014·Molecular Neurobiology·H ZhangH Yang
Sep 27, 2014·Cellular and Molecular Neurobiology·Hai-Jian WuSheng Chen
May 26, 2016·Journal of Neuroinflammation·Marie-Eve TremblayDusica Maysinger
Apr 12, 2016·Molecular Nutrition & Food Research·Ryan M BradleyRobin E Duncan
Dec 20, 2014·PloS One·Sylvie Gory-FauréAnnie Andrieux
Feb 6, 2017·Cardiovascular Research·Jan Dudek, Christoph Maack
Aug 25, 2017·Antioxidants & Redox Signaling·Yulia Y TyurinaValerian E Kagan
Jan 10, 2019·Cells·Helena XicoyGerard J M Martens
Feb 28, 2018·Nature Communications·Tammy RyanScott D Ryan
Oct 17, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Uwe SchlattnerValerian E Kagan
May 28, 2019·Cells·Monica Vara-PerezPatrizia Agostinis
Dec 2, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Alexandra G MoyzisÅsa B Gustafsson
May 3, 2019·CNS Neuroscience & Therapeutics·Yan WangBingwei Lu
Jan 1, 2017·Cellular and Molecular Neurobiology·Caitlin B Pointer, Andis Klegeris
Oct 27, 2017·FEBS Letters·Writoban Basu BallVishal M Gohil
Jan 29, 2019·Neural Regeneration Research·Ulfuara ShefaYoungbuhm Huh
Dec 25, 2019·Biochemistry. Biokhimii︠a︡·G A ShilovskyM Y Vyssokikh
Aug 17, 2019·Cells·David P DannheisigAstrid S Pfister
Jun 15, 2019·Acta Neuropathologica·Jason R RichardsonAnumantha G Kanthasamy
Dec 31, 2019·Oxidative Medicine and Cellular Longevity·Alejandra Guillermina Miranda-DíazFermín Paul Pacheco-Moisés

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Parkinson's Disease & Autophagy

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms