Mitochondrial dynamics, mitophagy, and

Mitochondrial import protein pathway Mitochondrial fusion and fission pathways

iΔΨm, (OXPHOSh) Ca2+ Fusion ++++ (Cell differentiationi) N Internal signal β-barrel outer Opa1 SH ER sequence SH membrane precursors Mfn1/2 SH SH GTP GTP C Inner membrane and GTP GTP Outer membrane Matrix carrier precursors 22 70 GTP fusion (N-terminal presequences) 35 GTP 20 37 Tom complex 5 Sam complex Opa1 Cytosol Outer 6 Sam50 7 Mdm10 membrane DRP1 Fis1 Inner membrane fusion Tim8-Tim13 Mim 1 Tom40 Bax/Bak Outer membrane

HR2 regions S-S Tim9-Tim10 S-S Inner Erv1 95 A 54 mitochondrial S-S Reorganization Mia40 space 21 Fission sequestration 50 18 Tim22 Translocation Depolarization to meet iΔΨm ATP needs Tim23 KREBS Cycle NADH FADH2 17 Oxa1 Tim 22 complex Mia Mba1 Mdm I ATP 44 38 H+ II 17 H+ Inner membrane 16 +++ III ADP - Pi 18 Ribosome Oxa H+ IV mtHsp70 H+ ATP +++ Mge1 MPP Healthy Mitophagy Matrix Tim 23 complex

Mitophagy pathway Autophagy pathway Lysosomal hydroiase

Hypoxia, Nutrient/Growth Rapamycin Starvation condition Ubiquitin Cytosol factor deprivation Lamp Stress Damaged mitochondrion Parkin Parkin iΔΨm Parkin MARF PINK1 PINK1 PINK1 Mfn1 VDAC1 Parkin AMPK mTOR Mfn2 PINK1 PINK1 Phagophore Autophagosome Autophagolyosome PARL LC3-II PINK1-L PINK1-S Parkin P FIS1 ATG13 ULK LC3-II Membrane PINK1 PINK1 FIP200 PINK1 MIRO2 P Bak PINK1 MIRO1 Parkin Parkin Parkin Cytoplasmic Cytosol proLC3 macromolecule LC3-II Atg4B Atg7/LC3-I Atg5/Atg12/Atg16 Organelle Atg9 PE Atg18 Atg2 Atg5/Atg12/Atg16 LC3-I Atg3/LC3-I LC3-II LC3-II LC3-II Mitochondrion LC3-II Autophagosome Autophagosome Autolysosome P13K III Atg16L PE LC3-II formation p150 Beclin1 Atg12 Fusion LC3-II Atg14 Atg5 LC3-II Atg10 Atg16L Atg5 p62 LC3-II Atg5 Phosphatidyl-ethanolamine Cathepsin Atg12 deactivation HDAC6 Mfn1 Cathepsin Bcl-2 Atg12 Atg10 MARF LC3-I Mfn2 Atg3 Wortmannin Atg7 Atg5 p62 3-Methyladenine Atg10 VDAC1 Atg12 Atg3 Lipase LC3-I Atg7 Cathepsin Atg7 Atg10 Lipase Atg7 Atg7 Atg12 Lysosome LC3-I

Atg7 Atg4 Atg12 LC3 To find out more, please visit www.abcam.com/mitochondrialdynamics

Copyright © 2018 Abcam, All rights reserved. This poster was made in collaboration with Michelangelo Campanella, Department of Comprarative Biomedical Sciences, The Royal Veterinary College, University of London. Mitochondrial dynamics, mitophagy, and autophagy

Mitochondrial import protein pathway Mitochondrial fusion and fission pathways

iΔΨm, (OXPHOSh) Ca2+ Fusion ++++ (Cell differentiationi) N Internal signal β-barrel outer Opa1 SH ER sequence SH membrane precursors Mfn1/2 SH SH GTP GTP C Inner membrane and GTP GTP Outer membrane Matrix carrier precursors 22 70 GTP fusion (N-terminal presequences) 35 GTP 20 37 Tom complex 5 Sam complex Opa1 Cytosol Outer 6 Sam50 7 Mdm10 membrane DRP1 Fis1 Inner membrane fusion Tim8-Tim13 Mim 1 Tom40 Bax/Bak apoptosis Outer membrane

HR2 regions S-S Tim9-Tim10 S-S Inner Erv1 95 A 54 mitochondrial S-S Reorganization Mia40 space 21 Fission sequestration 50 18 Tim22 Translocation Depolarization to meet iΔΨm ATP needs Tim23 KREBS Cycle NADH FADH2 17 Oxa1 Tim 22 complex Mia Mba1 Mdm I ATP 44 38 H+ II 17 H+ Inner membrane 16 +++ III ADP - Pi 18 Ribosome Oxa H+ IV mtHsp70 H+ ATP +++ Mge1 MPP Healthy mitochondrion Mitophagy Matrix Tim 23 complex

Mitophagy pathway Autophagy pathway Lysosomal hydroiase Lysosome

Hypoxia, Nutrient/Growth Rapamycin Starvation condition Ubiquitin Cytosol Parkin factor deprivation Lamp Stress Damaged mitochondrion Parkin Parkin iΔΨm Parkin MARF PINK1 PINK1 PINK1 Mfn1 VDAC1 Parkin AMPK mTOR Mfn2 PINK1 PINK1 Phagophore Autophagosome Autophagolyosome PARL LC3-II PINK1-L PINK1-S Parkin P FIS1 ATG13 ULK LC3-II Membrane PINK1 PINK1 FIP200 PINK1 MIRO2 P Bak PINK1 MIRO1 Parkin Parkin Parkin Cytoplasmic Cytosol proLC3 macromolecule LC3-II Atg4B Atg7/LC3-I Atg5/Atg12/Atg16 Organelle Atg9 PE Atg18 Atg2 Atg5/Atg12/Atg16 LC3-I Atg3/LC3-I LC3-II LC3-II LC3-II Mitochondrion LC3-II Autophagosome Autophagosome Autolysosome P13K III Atg16L PE LC3-II formation p150 Beclin1 Atg12 Fusion LC3-II Atg14 Atg5 LC3-II Atg10 Atg16L Atg5 p62 LC3-II Atg5 Phosphatidyl-ethanolamine Cathepsin Atg12 deactivation HDAC6 Mfn1 Cathepsin Bcl-2 Atg12 Atg10 MARF LC3-I Mfn2 Atg3 Wortmannin Atg7 Atg5 p62 3-Methyladenine Atg10 VDAC1 Atg12 Atg3 Lipase LC3-I Atg7 Cathepsin Atg7 Atg10 Lipase Atg7 Atg7 Atg12 Lysosome LC3-I

Atg7 Atg4 Atg12 LC3 To find out more, please visit www.abcam.com/mitochondrialdynamics

Copyright © 2018 Abcam, All rights reserved. This poster was made in collaboration with Michelangelo Campanella, Department of Comprarative Biomedical Sciences, The Royal Veterinary College, University of London.