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Chimeric molecule for mediating mitochondrial targeted degradation based on autophagy mechanism and application thereof

A technology of mitochondria and chimeric molecules, applied in the direction of hybrid peptides, drug combinations, fusion polypeptides, etc., can solve problems such as inability to directly regulate intracellular mitochondria, side effects, etc.

Active Publication Date: 2020-07-31
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods cannot directly regulate the level of intracellular mitochondria, and the use of traditional drugs will also cause serious side effects

Method used

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  • Chimeric molecule for mediating mitochondrial targeted degradation based on autophagy mechanism and application thereof
  • Chimeric molecule for mediating mitochondrial targeted degradation based on autophagy mechanism and application thereof
  • Chimeric molecule for mediating mitochondrial targeted degradation based on autophagy mechanism and application thereof

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Embodiment 1

[0055] 1. Construction of MTL-LIR (Mitochondrial Targeted Degradation Chimeric Molecule) Expression Vector

[0056] In the present invention, four MTL-LIR chimeric molecules were designed: LIR-ActA, NLRX1-LIR, Tom20-LIR and LIR-Mff. where LIR-ActA is composed of LIR and Listeria effector protein ActA 313-338 Amino acid sequence fusion expression, NLRX1-LIR is composed of human NLR family protein NLRX1 1-86 Amino acid sequence and LIR fusion expression, Tom20-LIR is composed of human mitochondrial outer membrane protein Tom20 1-34 The amino acid sequence is fused with LIR, and LIR-Mff is composed of LIR and human mitochondrial fission protein Mff 297-316 Amino acid sequence fusion expression.

[0057] The amino acid sequences of each chimeric molecule are:

[0058] Amino acid sequence of LIR-ActA chimeric molecule (SEQ ID NO: 1):

[0059]

[0060] Amino acid sequence of NLRX1-LIR chimeric molecule (SEQ ID NO:2):

[0061]

[0062] Amino acid sequence of Tom20-LIR chi...

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Abstract

The invention discloses a chimeric molecule for mediating mitochondrial targeted degradation based on autophagy mechanism. The amino acid sequence of the chimeric molecule is shown by SEQ ID NO: 1 or2 or 3 or 4. The invention also discloses a nucleic acid molecule for encoding the chimeric molecule for mediating mitochondrial targeted degradation based on, an expression vector containing the nucleic acid molecule, and applications of the chimeric molecule, the nucleic acid molecule and the expression vector in targeted degradation of mitochondria. According to the chimeric molecule for mediating mitochondrial targeted degradation, through targeted degradation of intracellular mitochondria, it is proved that regulation and control of intracellular organelles at the cellular level are feasible, and reference is provided for targeted degradation of other organelles; the chimeric molecule disclosed realizes degradation of the intracellular mitochondria at a cellular level, and provides adrug research and development thought for treatment of diseases; and particularly, a certain treatment thought can also be provided for neurodegenerative diseases caused by PINK1-Parkin pathway mutation.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a chimeric molecule that mediates mitochondrial targeted degradation based on an autophagy mechanism and an application thereof. Background technique [0002] Mitochondria are ubiquitous organelles in eukaryotic cells that participate in respiration and energy metabolism, and are the most important energy source for various physiological activities in cells. Most cells in the human body obtain the energy needed to maintain their own metabolism through the oxidative phosphorylation of mitochondria. [0003] Mitochondria are organelles in constant dynamic change. Mitochondria realize the self-renewal of mitochondria through fusion and fission, as well as the process of mitophagy, so as to ensure the normal progress of various physiological functions of mitochondria. Mitophagy is a type of selective autophagy that is primarily responsible for the removal of dysfunctional or damaged mi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62C12N15/85A61K38/16A61K47/64A61P25/28A61P25/16A61P25/14
CPCC07K14/00C12N15/85A61K38/16A61K47/64A61P25/28A61P25/16A61P25/14C07K2319/00
Inventor 杨爱民梅礼刚
Owner CHONGQING UNIV
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