Uncovering the Localization and Function of a Novel Read-Through Transcript ‘ITOMM40-APOE/I’

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 1
• Main Authors: Chang, Shichen, Torii, Satoru, Inamo, Jun, Ishikawa, Kinya, Kochi, Yuta, Shimizu, Shigeomi
• Format: Journal Article
• Language: English
• Published: MDPI AG 01-12-2023
• Subjects: Genetic aspects; Genetic transcription; Membrane proteins; Mitochondria; Physiological aspects; Japan
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13010069

Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, TOMM40-APOE. With cDNA amplification from THP-1 cells, the TOMM40-APOE3 product was successfully generated. We also generated TOMM40-APOE4, another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability.