Multifunctional intracellular matrix metalloproteinases: implications in disease.

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Medicine

Background:

• Matrix metalloproteinases (MMPs) were initially identified as extracellular proteases.
• Recent discoveries highlight significant intracellular functions of MMPs.
• MMP-2's role in cleaving sarcomeric proteins during cardiac injury exemplifies intracellular activity.

Purpose of the Study:

• To review the intracellular mechanisms, localization, substrates, and roles of MMPs.
• To explore the involvement of intracellular MMPs in various pathological conditions.
• To discuss future research directions and therapeutic strategies targeting intracellular MMPs.

Main Methods:

• Literature review of studies on intracellular MMP functions.
• Analysis of reported subcellular localization of various MMPs.
• Examination of known MMP substrates and their roles in cellular processes.

Main Results:

• At least eleven MMPs, including MMP-1, -3, -7, -8, -9, -10, -11, -12, -14, -23, and -26, function intracellularly.
• These MMPs are found in diverse cellular compartments like the cytosol, sarcomere, mitochondria, and nucleus.
• Intracellular MMPs contribute to diseases such as cardiovascular renal disorders, inflammation, and malignancy, and possess antimicrobial effects.

Conclusions:

• Intracellular MMPs play diverse roles in cellular function and disease pathogenesis.
• MMPs can act via both protease-dependent and independent mechanisms intracellularly.
• Understanding intracellular MMPs is crucial for developing targeted therapies.