Not just protons: Chloride also activates lysosomal acidic hydrolases
Xinghua Feng1,2, Siyu Liu2,3, Haoxing Xu1,2,4
1Department of Neurology and Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
The Journal of Cell Biology
|May 16, 2023
Summary
Lysosomal enzymes need an acidic environment and high chloride levels for optimal function. The chloride/proton exchanger ClC-7 is crucial for establishing these necessary intralysosomal conditions.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Lysosomal hydrolases are essential for cellular waste degradation.
- Optimal activity of these enzymes is known to depend on the acidic lumen of lysosomes.
Purpose of the Study:
- To investigate the role of intralysosomal chloride concentration in lysosomal hydrolase activation.
- To identify the mechanism responsible for establishing high intralysosomal chloride levels.
Main Methods:
- Analysis of lysosomal enzyme activity under varying ionic conditions.
- Investigation of the function of the chloride/proton exchanger ClC-7 in lysosome acidification and chloride homeostasis.
Main Results:
- Lysosomal hydrolase activation requires not only an acidic lumen but also high intralysosomal chloride concentrations.
- The lysosomal chloride/proton exchanger ClC-7 was identified as the key transporter responsible for establishing high intralysosomal chloride levels.
Conclusions:
- High intralysosomal chloride concentration, in addition to acidity, is a critical factor for optimal lysosomal hydrolase activity.
- ClC-7 plays a dual role in maintaining lysosomal function by regulating both proton and chloride transport.
Related Concept Videos
01:22Lysosomal Hydrolases
3.9K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
01:01Acid Halides to Carboxylic Acids: Hydrolysis
2.8K
Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic...
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon–oxygen π bond along with the departure of a halide ion. A final proton transfer step yields carboxylic...
2.8K
01:31Lysosomes
19.3K
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
19.3K
01:28pH Regulation in Cells
6.2K
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
6.2K
01:19Reactions of Acid Anhydrides
4.3K
The reactions of acid anhydrides are analogous to the reactions of acid chlorides and proceed via a nucleophilic acyl substitution. They only differ in the identity of the leaving group. During an acid chloride reaction, the leaving group is a chloride ion, and the by-product is hydrochloric acid. However, in an acid anhydride reaction, the leaving group is a carboxylate ion, and the by-product is a carboxylic acid.
4.3K
01:18Carboxylic Acids to Acid Chlorides
7.1K
Carboxylic acids react with SOCl2 or PCl5 to form acid chlorides. Amongst the carboxylic acid derivatives, acid chlorides are the most reactive and synthetically important derivatives. They are useful reagents for Friedel–Crafts acylation of some aromatic compounds.
7.1K