Mitochondrial quality control in AMD: does mitophagy play a pivotal role?

  • Juha M. T. Hyttinen
  • Johanna Viiri
  • Kai Kaarniranta
  • Janusz Błasiak
Review

Abstract

Age-related macular degeneration (AMD) is the predominant cause of visual loss in old people in the developed world, whose incidence is increasing. This disease is caused by the decrease in macular function, due to the degeneration of retinal pigment epithelium (RPE) cells. The aged retina is characterised by increased levels of reactive oxygen species (ROS), impaired autophagy, and DNA damage that are linked to AMD pathogenesis. Mitophagy, a mitochondria-specific type of autophagy, is an essential part of mitochondrial quality control, the collective mechanism responsible for this organelle’s homeostasis. The abundance of ROS, DNA damage, and the excessive energy consumption in the ageing retina all contribute to the degeneration of RPE cells and their mitochondria. We discuss the role of mitophagy in the cell and argue that its impairment may play a role in AMD pathogenesis. Thus, mitophagy as a potential therapeutic target in AMD and other degenerative diseases is as well explored.

Keywords

Cell senescence Mitochondrial DNA damage Nrf2/PGC-1α axis Oxidative damage Ubiquitin 

Abbreviations

AMBRA1

Activating molecule in beclin-1-regulated autophagy

AMD

Age-related macular degeneration

AMPK

AMP-activated protein kinase

ARE

Antioxidant-binding element

Atg

Autophagy-related gene

DMT1

Divalent metal transporter 1

ER

Endoplasmic reticulum

FPN1

Ferroportin 1

FPF

Flavoprotein fluorescence

FtMt

Mitochondrial ferritin

Gp78

Glycoprotein 78

HDAC6

Histone deacetylase 6

HIF-1α

Hypoxia-inducible factor-1α

Hsp

Heat-shock protein

IMM

Inner mitochondrial membrane

Keap1

Kelch-like ECH-associated protein 1

LIR

MAPK1LC3-interacting region

MAM

Mitochondria-associated endoplasmic reticulum membrane

MAPK

Mitogen-activated protein kinase

MAPK1LC3

Microtubule-associated protein 1 light-chain 3

Mfn

Mitofusin

MMP

Mitochondrial membrane potential

MPT

Mitochondrial permeability transition

MRC

Mitochondrial respiratory chain

mtDNA

Mitochondrial DNA

mTORC1

Mammalian target of rapamycin complex 1

Mul1

Mitochondrial E3 ubiquitin ligase

Nrf2

Nuclear factor (erythroid-derived 2)-related factor 2

OMM

Outer mitochondrial membrane

PGC-1α

Peroxisome proliferator-activated receptor gamma coactivator-1α

PI3K

Phosphatidylinosotole-3-kinase

PINK1

Phosphatase and tensin homologue-induced putative kinase

POS

Photoreceptor outer segment

ROS

Reactive oxygen species

RGC

Retinal ganglion cell

RPE

Retinal pigment epithelium

SAMD

Senescence-associated mitochondrial dysfunction

SASP

Senescent-associated secretory phenotype

Sirt1

NAD-dependent deacetylase Sirtuin 1

Smurf1

SMAD-specific E3 ubiquitin protein ligase 1

SOD

Superoxide dismutase

SQSTM1/p62

Sequestosome1/p62

Tfam

Mitochondrial transcription factor A

TIM

Translocase of the inner mitochondrial membrane

TOM

Translocase of the outer mitochondrial membrane

Ub

Ubiquitin

VDAC

Voltage-dependent anion channel

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

The authors thank Mr. Thomas Dunlop for checking the language of the manuscript.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of OphthalmologyKuopio University HospitalKuopioFinland
  3. 3.Department of Molecular GeneticsUniversity of ŁódźŁódźPoland

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