Serhiy Pankiv

• Dahl, Anette Kathinka; Mann, Daniel; Lystad, Alf Håkon Lohsen; Sachse, Carsten; Simonsen, Anne Gjøen & Pankiv, Serhiy (2026). Characterizing the membrane recruitment domain of BDCPs and its role in gray platelet syndrome. Journal of Cell Biology. ISSN 0021-9525. 225(10). doi: 10.1083/jcb.202510098. Fulltekst i vitenarkiv
• Croce, Katherine R; Ng, Christopher; Pankiv, Serhiy; Albarran, Eddy; Langfelder, Peter & Jesus, Ana Ramos de [Vis alle 22 forfattere av denne artikkelen] (2025). A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy - PMC. Neuron. ISSN 0896-6273. 113(22), s. 3780–3797. doi: 10.1016/j.neuron.2025.08.018. Fulltekst i vitenarkiv Vis sammendrag

  The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington’s disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.

• Moncho, Laura Cristina Trachsel; Veroni, Chiara; Mathai, Benan John; Lapao, Ana Sofia Da Silva; Singh, Sakshi & Asp, Nagham Theres [Vis alle 9 forfattere av denne artikkelen] (2025). SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics. Journal of Cell Biology. ISSN 0021-9525. 224(5). doi: 10.1083/jcb.202404009. Fulltekst i vitenarkiv Vis sammendrag

  We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX-IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of Cox-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics.

• Pankiv, Serhiy; Dahl, Anette Kathinka; Aas, Aleksander; Andersen, Rosa Linn; Brech, Andreas & Holland, Petter [Vis alle 9 forfattere av denne artikkelen] (2024). BEACH domain proteins function as cargo-sorting adaptors in secretory and endocytic pathways. Journal of Cell Biology. ISSN 0021-9525. 223(12). doi: 10.1083/jcb.202408173. Fulltekst i vitenarkiv Vis sammendrag

  We identify BEACH domain–containing proteins (BDCPs) as novel membrane coat proteins involved in the sorting of transmembrane proteins (TMPs) on the trans-Golgi network and tubular sorting endosomes. The seven typical mammalian BDCPs share a predicted alpha-solenoid-beta propeller structure, suggesting they have a protocoatomer origin and function. We map the subcellular localization of seven BDCPs based on their dynamic colocalization with RAB and ARF small GTPases and identify five typical BDCPs on subdomains of dynamic tubular-vesicular compartments on the intersection of endocytic recycling and post-Golgi secretory pathways. We demonstrate that BDCPs interact directly with the cytosolic tails of selected TMPs and identify a subset of TMPs, whose trafficking to the plasma membrane is affected in cells lacking BDCP. We propose that the competitive binding of BDCPs and clathrin coat adaptors to the cytosolic tails of TMPs, followed by their clustering to distinct subdomains of secretory/recycling tubules function as a mechanism for sorting of TMPs in pleomorphic tubular-vesicular compartments that lack a clathrin coat.

• Søreng, Kristiane; Pankiv, Serhiy; Bergsmark, Camilla; Haugsten, Ellen Margrethe; Dahl, Anette Kathinka & Ballina, Laura R de la [Vis alle 9 forfattere av denne artikkelen] (2022). ALFY localizes to early endosomes and cellular protrusions to facilitate directional cell migration. Journal of Cell Science. ISSN 0021-9533. 135(4). doi: 10.1242/jcs.259138. Fulltekst i vitenarkiv Vis sammendrag

  ABSTRACT Cell migration is a complex process underlying physiological and pathological processes such as brain development and cancer metastasis. The autophagy-linked FYVE protein (ALFY; also known as WDFY3), an autophagy adaptor protein known to promote clearance of protein aggregates, has been implicated in brain development and neural migration during cerebral cortical neurogenesis in mice. However, a specific role of ALFY in cell motility and extracellular matrix adhesion during migration has not been investigated. Here, we reveal a novel role for ALFY in the endocytic pathway and in cell migration. We show that ALFY localizes to RAB5- and EEA1-positive early endosomes in a PtdIns(3)P-dependent manner and is highly enriched in cellular protrusions at the leading and lagging edge of migrating cells. We find that cells lacking ALFY have reduced attachment and altered protein levels and glycosylation of integrins, resulting in the inability to form a proper leading edge and loss of directional cell motility.

• Bindesbøll, Christian; Aas, Aleksander; Ogmundsdottir, Margret Helga; Pankiv, Serhiy; Reine, Trine M. & Zoncu, Roberto [Vis alle 7 forfattere av denne artikkelen] (2020). NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease. Scientific Reports. 10(1). doi: 10.1038/s41598-020-61352-0. Fulltekst i vitenarkiv Vis sammendrag

  Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease. Here, we identify the large and poorly characterized BEACH domain protein Neurobeachin-like (NBEAL) 1 as a Golgi- associated protein required for regulation of cholesterol metabolism. NBEAL1 is most abundantly expressed in arteries. Genetic variants in NBEAL1 are associated with decreased expression of NBEAL1 in arteries and increased risk of coronary artery disease in humans. We show that NBEAL1 regulates cholesterol metabolism by modulating LDLR expression in a mechanism involving interaction with SCAP and PAQR3 and subsequent SREBP2-processing. Thus, low expression of NBEAL1 may lead to increased risk of coronary artery disease by downregulation of LDLR levels.

• Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lystad, Alf Håkon; Bindesbøll, Christian & Brenne, Hanne Britt [Vis alle 14 forfattere av denne artikkelen] (2019). NIPSNAP1 and NIPSNAP2 act as “eat-me signal” for mitophagy. Developmental Cell. ISSN 1534-5807. 49(4), s. 509–525.e12. doi: 10.1016/j.devcel.2019.03.013. Fulltekst i vitenarkiv Vis sammendrag

  The clearance of damaged or dysfunctional mitochondria by selective autophagy (mitophagy) is important for cellular homeostasis and prevention of disease. Our understanding of the mitochondrial signals that trigger their recognition and targeting by mitophagy is limited. Here, we show that the mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) and NIPSNAP2 accumulate on the mitochondria surface upon mitochondrial depolarization. There, they recruit proteins involved in selective autophagy, including autophagy receptors and ATG8 proteins, thereby functioning as an “eat me” signal for mitophagy. NIPSNAP1 and NIPSNAP2 have a redundant function in mitophagy and are predominantly expressed in different tissues. Zebrafish lacking a functional Nipsnap1 display reduced mitophagy in the brain and parkinsonian phenotypes, including loss of tyrosine hydroxylase (Th1)-positive dopaminergic (DA) neurons, reduced motor activity, and increased oxidative stress.

• Abudu, Yakubu Princely; Pankiv, Serhiy; Mathai, Benan John; Lamark, Trond; Johansen, Terje & Simonsen, Anne (2019). NIPSNAP1 and NIPSNAP2 act as “eat me” signals to allow sustained recruitment of autophagy receptors during mitophagy. Autophagy. ISSN 1554-8627. doi: 10.1080/15548627.2019.1637642. Fulltekst i vitenarkiv
• Søreng, Kristiane; Munson, Michael Joseph; Lamb, Christopher R.; Bjørndal, Gunnveig Toft; Pankiv, Serhiy & Carlsson, Sven R. [Vis alle 8 forfattere av denne artikkelen] (2018). SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2. EMBO Reports. ISSN 1469-221X. 19:e44837(4), s. 1–12. doi: 10.15252/embr.201744837. Fulltekst i vitenarkiv Vis sammendrag

  Trafficking of mammalian ATG9A between the Golgi apparatus, endosomes and peripheral ATG9A compartments is important for autophagosome biogenesis. Here, we show that the membrane remodelling protein SNX18, previously identified as a positive regulator of autophagy, regulates ATG9A trafficking from recycling endosomes. ATG9A is recruited to SNX18‐induced tubules generated from recycling endosomes and accumulates in juxtanuclear recycling endosomes in cells lacking SNX18. Binding of SNX18 to Dynamin‐2 is important for ATG9A trafficking from recycling endosomes and for formation of ATG16L1‐ and WIPI2‐positive autophagosome precursor membranes. We propose a model where upon autophagy induction, SNX18 recruits Dynamin‐2 to induce budding of ATG9A and ATG16L1 containing membranes from recycling endosomes that traffic to sites of autophagosome formation.

• Holland, Petter; Knævelsrud, Helene; Søreng, Kristiane; Mathai, Benan John; Lystad, Alf Håkon & Pankiv, Serhiy [Vis alle 16 forfattere av denne artikkelen] (2016). HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nature Communications. 7. doi: 10.1038/ncomms13889. Fulltekst i vitenarkiv Vis sammendrag

  A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.

• Lystad, Alf Håkon; Ichimura, Yoshinobu; Takagi, K; Yang, Yinjie; Pankiv, Serhiy & Kanegae, Yumi [Vis alle 12 forfattere av denne artikkelen] (2014). Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures. EMBO Reports. ISSN 1469-221X. 15(5), s. 557–565. doi: 10.1002/embr.201338003. Fulltekst i vitenarkiv
• Lång, Emma Helena; Grudic, Amra; Pankiv, Serhiy; Bruserud, Øystein; Simonsen, Anne & Bjerkvig, Rolf [Vis alle 8 forfattere av denne artikkelen] (2012). The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling. Blood. ISSN 0006-4971. 120(4), s. 847–857. doi: 10.1182/blood-2011-10-388496. Fulltekst i vitenarkiv
• Ravuri, Chandra Sekhar; Svineng, Gunbjørg; Pankiv, Serhiy & Huseby, nils-erik (2011). Endogenous production of reactive oxygen species by the NADPH oxidase complexes is a determinant of gamma gamma-glutamyltransferase expression. Free radical research. ISSN 1071-5762. 45(5), s. 600–610. doi: 10.3109/10715762.2011.564164. Fulltekst i vitenarkiv
• Pankiv, Serliy; Lamark, Trond; Bruun, Jack-Ansgar; Øvervatn, Aud Karin; Bjørkøy, Geir & Johansen, Terje (2010). Nucleocytoplasmic Shuttling of p62/SQSTM1 and Its Role in Recruitment of Nuclear Polyubiquitinated Proteins to Promyelocytic Leukemia Bodies. Journal of Biological Chemistry. ISSN 0021-9258. 285(8), s. 5941–5953. doi: 10.1074/jbc.M109.039925. Fulltekst i vitenarkiv
• Pankiv, Serliy; Alemu, Endalkachew; Brech, Andreas; Bruun, Jack-Ansgar; Lamark, Trond & Øvervatn, Aud Karin [Vis alle 8 forfattere av denne artikkelen] (2010). FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. Journal of Cell Biology. ISSN 0021-9525. 188(2), s. 253–269. doi: 10.1083/jcb.200907015. Fulltekst i vitenarkiv Vis sammendrag

  Autophagy is the main eukaryotic degradation pathway for long-lived proteins, protein aggregates, and cytosolic organelles. Although the protein machinery involved in the biogenesis of autophagic vesicles is well described, very little is known about the mechanism of cytosolic transport of autophagosomes. In this study, we have identified an adaptor protein complex, formed by the two autophagic membrane-associated proteins LC3 and Rab7 and the novel FYVE and coiled-coil (CC) domain-containing protein FYCO1, that promotes microtubule (MT) plus end-directed transport of autophagic vesicles. We have characterized the LC3-, Rab7-, and phosphatidylinositol-3-phosphate-binding domains in FYCO1 and mapped part of the CC region essential for MT plus end-directed transport. We also propose a mechanism for selective autophagosomal membrane recruitment of FYCO1.

• Bjørkøy, Geir; Lamark, Trond; Pankiv, Serliy; Øvervatn, Aud Karin; Brech, Andreas & Johansen, Terje (2009). MONITORING AUTOPHAGIC DEGRADATION OF P62/SQSTM1. Methods in Enzymology. ISSN 0076-6879. 452, s. 181–197. doi: 10.1016/S0076-6879(08)03612-4. Fulltekst i vitenarkiv
• Pankiv, Serliy; Clausen, Terje; Lamark, Trond; Brech, A; Bruun, Jack-Ansgar & Outzen, heidi [Vis alle 9 forfattere av denne artikkelen] (2007). p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. Journal of Biological Chemistry. ISSN 0021-9258. 282, s. 24131–24145. doi: 10.1074/jbc.M702824200. Fulltekst i vitenarkiv
• MØller, seila; Pankiv, Serliy; Johannessen, Mona; Moens, Ugo & Huseby, nils-erik (2007). gamma-Glutamyltransferase is upregulated after oxidative stress through the Ras signal transduction pathway in rat colon carcinoma cells. Free radical research. ISSN 1071-5762. 41(12), s. 1376–1384. Fulltekst i vitenarkiv
• Pankiv, Serliy; Møller, Seila; Bjørkøy, Geir; Moens, Ugo & Huseby, Nils-Erik (2006). Radiation-induced upregulation of gamma-glutamyltransferase in colon carcinoma cells is mediated through the Ras signal transduction pathway. Biochimica et Biophysica Acta - General Subjects. ISSN 0304-4165. 1760. Fulltekst i vitenarkiv

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• Pankiv, Serhiy & Johansen, Terje (2010). FYCO1 Linking autophagosomes to microtubule plus end-directing molecular motors. Autophagy. ISSN 1554-8627. 6(4), s. 550–552. Fulltekst i vitenarkiv
• Bjørkøy, Geir; Lamark, Trond; Pankiv, Serliy; Brech, A; Outzen, heidi & Perander, maria [Vis alle 9 forfattere av denne artikkelen] (2006). P62/SQSTM1: A direct link betwwen polyubiquitinated preotein aggregates and LC3. Fulltekst i vitenarkiv
• Bjørkøy, Geir; Lamark, Trond; Pankiv, Serliy; Brech, A; Outzen, heidi & Perander, maria [Vis alle 9 forfattere av denne artikkelen] (2006). P62/SQSTM1: A direct link betwwen polyubiquitinated preotein aggregates and LC3. Fulltekst i vitenarkiv
• Bjørkøy, Geir; Lamark, Trond; Pankiv, Serliy; Brech, A; Outzen, heidi & Øvervatn, Aud [Vis alle 8 forfattere av denne artikkelen] (2006). p62 as a direct link between protein aggregates and the autophgic machinery. Fulltekst i vitenarkiv
• Bjørkøy, Geir; Lamark, Trond; Pankiv, Serliy; Brech, A; Outzen, heidi & Perander, maria [Vis alle 9 forfattere av denne artikkelen] (2006). P62/SQSTM1: A direct link betwwen polyubiquitinated preotein aggregates and LC3. Fulltekst i vitenarkiv
• Johansen, Terje & Pankiv, Serhiy (2009). p62/SQSTM1 and FYCO1: novel interaction partners of LC3 involved in autophagy. UiT Norges arktiske universitet. Fulltekst i vitenarkiv

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