A proteomic screen with Drosophila Opa1-like identifies Hsc70-5/Mortalin as a regulator of mitochondrial morphology and cellular homeostasis.

Abstract

Mitochondrial morphology is regulated by conserved proteins involved in fusion and fission processes. The mammalian Optic atrophy 1 (OPA1) that functions in mitochondrial fusion is associated with Optic Atrophy and has been implicated in inner membrane cristae remodeling during cell death. Here, we show Drosophila Optic atrophy 1-like (Opa1-like) influences mitochondrial morphology through interaction with 'mitochondria-shaping' proteins like Mitochondrial assembly regulatory factor (Marf) and Drosophila Mitofilin (dMitofilin). To gain an insight into Opa1-like's network, we delineated bonafide interactors like dMitofilin, Marf, Serine protease High temperature requirement protein A2 (HTRA2), Rhomboid-7 (Rho-7) along with novel interactors such as Mortalin ortholog (Hsc70-5) from Drosophila mitochondrial extract. Interestingly, RNAi mediated down-regulation of hsc70-5 in Drosophila wing imaginal disc's peripodial cells resulted in fragmented mitochondria with reduced membrane potential leading to proteolysis of Opa1-like. Increased ecdysone activity induced dysfunctional fragmented mitochondria for clearance through lysosomes, an effect enhanced in hsc70-5 RNAi leading to increased cell death. Over-expression of Opa1-like rescues mitochondrial morphology and cell death in prepupal tissues expressing hsc70-5 RNAi. Taken together, we have identified a novel interaction between Hsc70-5/Mortalin and Opa1-like that influences cellular homeostasis through mitochondrial fusion.

• Authors: Shamik Banerjee, Balaji Chinthapalli
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 54 Pg. 36-48 (Sep 2014) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 24998521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Drosophila Proteins
• HSC70 Heat-Shock Proteins
• HSP70 Heat-Shock Proteins
• Membrane Proteins
• Mitochondrial Proteins
• OPA1 protein, Drosophila
• RNA, Messenger
• mortalin

Topics

• Animals
• Apoptosis
• Blotting, Western
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Drosophila Proteins (genetics, metabolism)
• Drosophila melanogaster (genetics, growth & development, metabolism)
• Gene Expression Regulation, Developmental
• HSC70 Heat-Shock Proteins (genetics, metabolism)
• HSP70 Heat-Shock Proteins (genetics, metabolism)
• Hemocytes (metabolism)
• Homeostasis (physiology)
• Immunoenzyme Techniques
• Immunoprecipitation
• Larva (genetics, growth & development, metabolism)
• Membrane Potential, Mitochondrial
• Membrane Proteins (genetics, metabolism)
• Mitochondria (chemistry, metabolism)
• Mitochondrial Proteins (genetics, metabolism)
• Proteomics (methods)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization