The chemical bonds that maintain the three-dimensional structure of proteins are relatively weak. They will break in the presence of high temperatures, ions and organic solvents, thus changing the protein shape. Loss of protein structure results in loss of function.
High temperature: it makes the atoms vibrate more violently and the water molecules hit the protein more strongly, thus breaking the chemical bonds of the protein. As the temperature increases, van der Waals interactions are disrupted first, followed by hydrophobic interactions, hydrogen and ionic bonds, and finally disulfide and peptide bonds.
PH: If the PH does not change much, then the electrostatic interactions are smaller than those of other interactions that stable proteins, so they do not denature. But if they are in the extreme PH, the protein charge distribution will change drastically, which will destroy the structure of protein. For example, if the PH drops to 1, the protonated amino groups take on a complete positive charge. They are more attractive than partially charged hydrogen bonds, and those partial negative charged groups are attracted to them causing hydrogen bond to be damaged. And the carboxyl groups with one negative charge are neutralized by hydrogen ions. Those positive charged groups that are attracted to the carboxyl group will stay away.
High concentration of salt solutions (non-heavy metals): adding a lot of salt into a protein solution will cause it to precipitate. Large amounts of salt ions compete with the proteins for water molecules: salt ions bind to the water molecules around protein to make them dehydrated; some salt ions also bind to charged groups instead of water molecules.
Organic solvents and detergents: Their hydrophobic groups alter the protein structure by disrupting their intramolecular hydrophobic interactions. Those hydrophobic groups buried deeply in the core tend to be exposed to organic solvents or detergents, which cause the folded protein molecules to unravel. Such changes are usually drastic and irreversible.
Denaturation is reversible, if the factors that cause denaturation are withdrawn and proteins regain their original structure and function. Whether it is reversible or not is closely related to the complexity of proteins and the degree of structural change. The simpler structure and milder change, the greater likelihood that the proteins will revert to their original state. Some complex proteins cannot form their own structures spontaneously and they need the help of other molecules. Their denaturation is often irreversible.