Topological characterization of the mitochondrial phospholipid scramblase 3

Author(s)

Luevano-Martinez, Luis Alberto ^{[1, 2]} ; Kowaltowski, Alicia J. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Av Lineu Prestes 1374, BR-05508900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: FEBS Letters; v. 591, n. 24, p. 4056-4066, DEC 2017.
• Web of Science Citations: 0

Abstract

Scramblases redistribute phospholipids in biological membranes. Phospholipid scramblase 3 (PLSCR3), which is located in mitochondria, has been reported to be involved in cardiolipin distribution from the inner to the outer membrane, thus regulating cellular processes such as apoptosis or mitophagy. However, the localization and topology of this protein has not been convincingly addressed to support a role in intermembrane phospholipid transfer. Here, we studied PLSCR3 topology within mitochondria. We show that PLSCR3 inserts in the inner membrane (IM) via its C-terminal transmembrane helix, whereas its N-terminal portion is oriented toward the intermembrane space where it is activated by calcium. Our results suggest that PLSCR3, via its C-terminal transmembrane domain, participates in the bidirectional movement of phospholipids within the IM. (AU)

• FAPESP's process: 16/12999-0 - Evolution of the cardiolipin biosynthetic pathway: biochemical implications for the evolution of the Eukarya domain
• Grantee: Luis Alberto Luevano Martinez
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/04919-9 - Evaluation of the adaptive response of mitochondrial membranes to stress: role of cardiolipin in membrane plasticity, dynamics and pathological situations
• Grantee: Luis Alberto Luevano Martinez
• Support type: Scholarships in Brazil - Post-Doctorate