My research focuses on the molecular and cellular mechanisms of selective autophagy, mitophagy, and cell signaling, and how defects in these processes contribute to neurodegenerative diseases and cancer. Selective autophagy is a cellular quality-control system that removes damaged, surplus, or unwanted proteins, lipids, and organelles. By maintaining cellular homeostasis, this process is essential for healthy cell function. When autophagy is impaired or dysregulated, it can contribute to diseases including Parkinson’s disease, other neurodegenerative disorders, and cancer.

A major focus of my research has been mitophagy, the selective removal of damaged or surplus mitochondria. Mitochondria are essential for energy production and cellular signaling, but damaged mitochondria can generate harmful stress and contribute to neuronal dysfunction. Understanding how cells identify and eliminate defective mitochondria is therefore particularly important for understanding Parkinson’s disease and other neurodegenerative conditions.

My work contributed to the discovery that NIPSNAP1 and NIPSNAP2 function as “eat-me” signals on damaged mitochondria. These proteins help mark mitochondria for recognition by autophagy receptors and support the sustained recruitment of the autophagy machinery during mitophagy. I have also contributed to the discovery that SAMM50 acts as a receptor in piecemeal mitophagy, a process that enables cells to selectively remove damaged or surplus components of mitochondria rather than eliminating the entire organelle. These findings have advanced our understanding of how mitochondrial quality control is regulated and how its failure may contribute to neurodegenerative disease.

My research has also examined the regulation of autophagy through signaling pathways and autophagy receptors. This includes work on TBK1-dependent signaling, ATG8-family proteins, SNARE proteins, lysosomal damage, mTOR regulation, and the molecular mechanisms that control the initiation and selectivity of autophagy. In addition, my research has contributed to the broader development and interpretation of experimental methods used to monitor autophagy.

Another important area of my work concerns the relationship between mitophagy and cancer treatment. Many anticancer drugs damage mitochondria to induce apoptosis and eliminate cancer cells. However, cancer cells can rapidly activate mitophagy to remove drug-damaged mitochondria. This protective response can help cancer cells survive treatment and may contribute to drug resistance. My current research in this area investigates the mechanisms of drug-induced mitophagy and seeks to determine whether this pathway can be targeted to improve the effectiveness of cancer therapies.

My current work also focuses on epithelial-to-mesenchymal transition (EMT) in breast cancer. EMT is a cellular process associated with changes in cell identity, migration, invasion, metastasis, and treatment response. As project leader, I am investigating the molecular and cellular mechanisms that regulate EMT and how these processes interact with autophagy, mitochondrial quality control, and cell signaling. This research aims to improve our understanding of breast cancer progression and identify potential strategies for making cancer treatment more effective.

Across these research areas, I combine molecular and cellular biology with advanced imaging approaches, including fluorescence nanoscopy. This interdisciplinary approach allows me to investigate autophagy, mitophagy, mitochondrial dynamics, and cancer-associated cell signaling with high spatial and molecular resolution. Overall, my research seeks to explain how cells maintain quality control, how these systems become disrupted in disease, and how they can be therapeutically targeted in neurodegenerative diseases and cancer.

Basic research into the cellular- and molecular mechanisms of selective autophagy and cell signaling relevant for cancer, neurodegenerative diseases, aging, inflammation and host defense against intracellular pathogens. Terje and his group made a major breakthrough in our understanding of selective autophagy by discovering the first selective autophagy receptor p62/SQSTM1 and elucidated how specificity in cargo selection (waste disposal) could be achieved and how autophagy receptors could connect the cargo (waste) to the forming autophagosome. Some main discoveries by Terje and co-workers in the Autophagy Research Group are:

• Discovered the first selective autophagy receptors p62/SQSTM1 and NBR1

• Showed that the selective autophagy receptors bound to cargo and to Atg8 family proteins

• Identified the LIR (LC3 Interacting Region) motif mediating the interaction in the majority of Atg8 interacting proteins

• Discovered p62 formed protein bodies inside cells that are degraded by autophagy

• Developed a novel tandem tag fluorescent protein assay to monitor autophagic flux

• Described the positive feedback loop regulation between p62 and NRF2

• Found NBR1 as the selective autophagy receptor in plants

• Discovered NBR1 acting as a pexophagy receptor

• Discovered the first Golgiphagy receptor, CALCOCO1, also acting in ERphagy

• Showed Atg8 family proteins to act as membrane-bound scaffolds for autophagy core machinery proteins including the ULK1/2 complexes, the PI3K class III complex and ATG4 proteins.

• Showed NIPSNAP1 and NIPSNAP2 to act as "Eat Me" signals for Mitophagy

• Discovered that FKBP8 can act as a mitophagy receptor and that SAMM50 is involved in basal and OXPHOS-induced mitophagy

• Found the inflammation repressor TNIP1/ABIN-1 to be degraded by autophagy following TBK1 activation.
• Discovered MORG1 as a new negative regulator of mTORC1 allowing basal selective autophagy in nutrient rich conditions.

Keywords: Selective autophagy receptors, ATG8 family proteins, LIR motifs, aggrephagy, mitophagy, ER-phagy, Golgiphagy

Neuropharmacotoxicology.

The main goal of the research group (including Trond) is to understand the molecular mechanisms utilized by cells to cope with stress, under normal conditions and in disease. The discovery of the first selective autophagy receptors in 2005 led the research into the autophagy field, and autophagy soon became their main interest. Autophagy was at that time considered a basically non-selective process and the pathological importance of autophagy was not fully realized. The identification of the first selective autophagy receptors coincided with an increased interest in autophagy research worldwide. The following research (including work by the autophagy research group) revealed the process to be highly selective. It soon became evident that reduced selective autophagy is associated with aging, and is implicated in several age-related pathologies, including neurodegenerative diseases, cancer, and inflammation. Our understanding of selective autophagy is now at a different level compared to 20 years ago, but several important knowledge gaps exist, and the remaining goal is to fill these gaps with new knowledge.