Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation.
EMBO reports, (2017).
Abreu, S., Kriegenburg, F., Gomez-Sanchez, R., Mari, M., Sanchez-Wandelmer, J., Skytte Rasmussen, M., Soares Guimaraes, R., Zens, B., Schuschnig, M., Hardenberg, R., Peter, M., Johansen, T., Kraft. C., Martens, S., Reggiori, F. 
Beyond Atg8 binding: the role of AIM/LIR motifs in autophagy.
Autophagy, (2017).
Fracchiolla, D., Sawa-Makarska, J., and Martens, S.

In this commentary to the eLife paper below we discuss the dual roles of LIR motifs in autophagy. In particular, we speculate that LIR motifs may also be involved in the recruitment of the autophagy machinery to the cargo. Thus these motifs may have roles upstream of Atg8 protein binding. The picture on the right was hand drawn by Dorotea.

Section image
Mechanism of cargo-directed Atg8 conjugation during selective autophagy.
eLife 5, e18544. (2016).
Fracchiolla, D., Sawa-Makarska, J., Zens, B., de Ruiter, A., Zaffagnini, G., Brezovich, A., Romanov, J., Runggatscher, K., Kraft, C., Zagrovic, B., and Martens, S.   

In this paper we show that the yeast cargo receptor Atg19 directly interacts with the E3-like Atg12–Atg5-Atg16 complex via its LIR motifs. The receptor thereby recruits the E3 to prApe1 to locally stimulate Atg8 conjugation to phosphatidylethanolamine (PE) in the membrane. In a fully reconstituted system we show that these interactions are sufficient to mediate Atg8 conjugation at the cargo. The recruitment of the E3-like Atg12–Atg5-Atg16 complex to cargo material may be a conserved mechanism since we show that also human cargo receptors bind the ATG5 protein.


Section image
No ATG8s, no problem? How LC3/GABARAP proteins contribute to autophagy.
Journal of Cell Biology (2016). 
Martens, S.
In Vitro Reconstitution of Atg8 Conjugation and Deconjugation.
Methods in Enzymology. (2016)
Fracchiolla, D., B. Zens, and S. Martens
Phospholipids in Autophagosome Formation and Fusion.
Journal of Molecular Biology. (2016).
Martens, S., Nakamura, S., and Yoshimori, T.
Insights into autophagosome biogenesis from in vitro reconstitutions.
Journal of Structural Biology. (2016).
Turco, E., and Martens, S. 
Necessary, but also Sufficient?
Trends in Cell Biology (2016).
Martens, S. 
Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria.
Proceedings of the National Academy of Sciences. (2016)
Richter, B., Sliter, D.A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S.A., Youle, R.J., and Dikic, I. 
Mechanisms of selective autophagy
J Mol Biol, 10.1016/j.jmb.2016.02.004 (2016)
Zaffagnini G, Martens S
Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy.
eLife 2015;10.7554/eLife.08941 (2015)
Wurzer B, Zaffagnini G, Fracchiolla D, Turco E, Abert C, Romanov J, Martens S

Using fluorescently labeled proteins combined with imaging-based techniques we show that the human autophagic cargo receptor p62/SQSTM-1 employs oligomerization to accumulate at ubiquitin-covered cargo material. In vivo this activity is required for p62 to localize to intracellular Salmonella. At the same time oligomerization mediates avid binding to the autophagosomal membrane via its interaction with ATG8-family proteins.  We further show in a reconstituted system that p62 is able to mediate membrane bending around cargo material.

Section image
How cells coordinate waste removal through their major proteolytic pathways.
NAT CELL BIOL; 17(7):841-2.(2015).
Martens S, Bachmair A.
In vitro systems for Atg8 lipidation.
Methods 75:37-43. March 2015
Zens B, Sawa-Makarska J, Martens S
Excluding the unwanted during autophagy.
Cell Cycle. 13(15):2313-4.(2014).
Sawa-Makarska J, Martens S.
Hrr25 kinase promotes selective autophagy by phosphorylating the cargo receptor Atg19.
EMBO Rep. 15(8):862-70.(2014).
Pfaffenwimmer T, Reiter W, Brach T, Nogellova V, Papinski D, Schuschnig M, Abert C, Ammerer G, Martens S, Kraft C.


Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane-cargo apposition during selective autophagy.
NAT CELL BIOL;5(16):425-33.(2014).
Sawa-Makarska, Justyna; Abert, Christine; Romanov, Julia; Zens, Bettina; Ibiricu, Iosune; Martens, Sascha.

In this paper we show that the Atg19 cargo receptor contains multiple interaction sites for the Atg8 protein in its C-terminus. Atg8 proteins decorate the autophagosomal membrane and collectively these multiple interaction sites for Atg8 mediate the bending of the membrane around autophagic cargo material. In vivo the close apposition of the autophagosomal membrane and the cargo will exclude non-cargo material from its delivery into the lysosomal system.

See also comments in Current Biology and Nature Cell Biology:

Autophagy: close contact keeps out the uninvited.

Selective autophagy goes exclusive.

Section image
Autophagy at sea.
Autophagy. 9(9):1286-91.(2013).
Martens S, Rusten TE, Kraft C.
Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation.
EMBO J;31(22):4304-17. (2012)
Romanov, Julia; Walczak, Marta; Ibiricu, Iosune; Schüchner, Stefan; Ogris, Egon; Kraft, Claudine; Martens, Sascha.

imgres   In this paper we show how the conserved Atg5-Atg12/Atg16 complex binds to membranes and how this is regulated. In addition we elucidate the function of membrane binding by this complex during autophagosome formation. In particular we find that the membrane binding by the Atg5-Atg12/Atg16 complex is required for membrane tethering and Atg8 conjugation to the membrane lipid phosphatidylethanolamine. This is the first paper describing the reconstitution of autophagic processes using giant unilamellar vesicles.

Mechanisms and regulation of autophagosome formation.
CURR OPIN CELL BIOL;24(4):496-501. (2012).
Kraft,C., Martens, S.
C2 domains and membrane fusion.
Curr Top Membr. 68:141-59.(2011).
Martens S, McMahon HT.
Forming giant vesicles with controlled membrane composition, asymmetry, and contents.
Proc Natl Acad Sci U S A.108(23):9431-6.(2011).
Richmond DL, Schmid EM, Martens S, Stachowiak JC, Liska N, Fletcher DA.
The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii.
BMC Biol. Jan 28;9:7.(2011).
Pawlowski N, Khaminets A, Hunn JP, Papic N, Schmidt A, Uthaiah RC, Lange R, Vopper G, Martens S, Wolf E, Howard JC.
Membrane curvature in synaptic vesicle fusion and beyond.
Cell. 140(5):601-5.(2010).
McMahon HT, Kozlov MM, Martens S.
Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release.
Science. 327(5973):1614-8.(2010).
Groffen AJ, Martens S, Díez Arazola R, Cornelisse LN, Lozovaya N, de Jong AP, Goriounova NA, Habets RL, Takai Y, Borst JG, Brose N, McMahon HT, Verhage M.
Role of C2 domain proteins during synaptic vesicle exocytosis.
Biochem Soc Trans. 38(Pt 1):213-6.(2010).
Martens S.
HIV-1 Nef membrane association depends on charge, curvature, composition and sequence.
Nat Chem Biol. 6(1):46-53.(2010).
Gerlach H, Laumann V, Martens S, Becker CF, Goody RS, Geyer M.
Synaptotagmin-1 utilizes membrane bending and SNARE binding to drive fusion pore expansion.
Mol Biol Cell. 19(12):5093-103.(2008).
Lynch KL, Gerona RR, Kielar DM, Martens S, McMahon HT, Martin TF.
Regulatory interactions between IRG resistance GTPases in the cellular response to Toxoplasma gondii.
EMBO J. 27(19):2495-509.(2008).
Hunn JP, Koenen-Waisman S, Papic N, Schroeder N, Pawlowski N, Lange R, Kaiser F, Zerrahn J, Martens S, Howard JC.
Mechanisms of membrane fusion: disparate players and common principles.
Nat Rev Mol Cell Biol. 9(7):543-56.(2008).
Martens S, McMahon HT.
Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling.
Nature. 449(7164):923-7.(2007).
Daumke O, Lundmark R, Vallis Y, Martens S, Butler PJ, McMahon HT.
How synaptotagmin promotes membrane fusion.
Science. 316(5828):1205-8.(2007).
Martens S, Kozlov MM, McMahon HT.
The interferon-inducible GTPases.
Annu Rev Cell Dev Biol. 22:559-89.(2006).
Martens S, Howard J.
Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases.
PLoS Pathog. 1(3):e24.(2005).
Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC.
The many layers of immunity.
Genome Biol. 3(8):REPORTS4025. (2002).
Martens S.