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Apoptosis

, Volume 20, Issue 5, pp 621–634 | Cite as

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

  • Tina Garofalo
  • Valeria Manganelli
  • Maria Grasso
  • Vincenzo Mattei
  • Alberto Ferri
  • Roberta Misasi
  • Maurizio SoriceEmail author
THE ROLE OF SPHINGOLIPIDS AND LIPID RAFTS IN DETERMINING CELL FATE

Abstract

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER–mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington’s chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies.

Keywords

Lipid rafts Microdomains GD3 Mitochondria Apoptosis 

Abbreviations

ALS

Amyotrophic lateral sclerosis

Bax

Bcl-2-like protein 4

Bid

BH3 interacting-domain death agonist

CL

Cardiolipin

CLIPR-59

Cytoplasmic linker proteins-59

DAMP

Danger-associated molecular pattern

DLP1/Drp1

Dynamin-like protein-1

[D]-PDMP

(±)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol hydrochloride

ER

Endoplasmic reticulum

fALS

Familial form of ALS

GSK-3b

Glycogen synthase kinase-3b

HD

Huntington disease

hFis1

Mitochondrial fission 1 protein

Htt

Huntingtin

IP3R-1

Inositol-1,4,5-tris-phosphate receptor

MAM

Mitochondria-associated membrane

MßCD

Methyl ß-cyclodextrin

Mfn2

Mitofusin-2

OMM

Outer mitochondrial membrane

OPA1

Optic Atrophy 1

PrPC

Cellular prion protein

PrPSc

Conformationally altered isoform of prionic protein

PTPIP51

Protein tyrosine phosphatase interacting protein 51

Sig1R

Sigma1 receptor

SOD1

Superoxide dismutase 1

t-Bid

Truncated bid

TDP43

Transactive response DNA binding protein 43

VAPB

Vesicle-associated membrane protein-associated protein B

VDAC-1

Voltage-dependent anion channel-1

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Tina Garofalo
    • 1
  • Valeria Manganelli
    • 1
  • Maria Grasso
    • 1
  • Vincenzo Mattei
    • 2
  • Alberto Ferri
    • 3
  • Roberta Misasi
    • 1
  • Maurizio Sorice
    • 1
    • 2
    Email author
  1. 1.Department of Experimental MedicineSapienza University of RomeRomeItaly
  2. 2.Laboratory of Experimental Medicine and Environmental PathologyUniversity Consortium “Sabina Universitas”RietiItaly
  3. 3.Institute of Cellular Biology and Neurobiology, CNRRomeItaly

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