Caseinolytic mitochondrial matrix peptidase chaperone subunit X (CLPX)

Caseinolytic mitochondrial matrix peptidase chaperone subunit X (CLPX) is a mitochondrial AAA+ ATPase enzyme and protein unfoldase that is an essential component of the ClpXP proteolytic complex. CLPX recognizes, unfolds, and translocates misfolded, damaged, or regulatory protein substrates into ClpP for degradation, playing a key role in mitochondrial protein quality control and cell stress responses[2][3]. In addition to degradation, CLPX in mitochondria can remodel target proteins in a non-proteolytic manner to regulate biosynthetic enzyme activation (such as activation of 5-aminolevulinate synthase for heme biosynthesis)[1]. Dysregulation of CLPX function is implicated in diseases related to mitochondrial dysfunction, neurodegeneration, aging, and certain cancers. CLPX recognizes substrates via phosphorylation marks, most notably phosphorylated serine residues, and is essential for mitochondrial health and viability in several biological contexts[2][3].

Other names

ATP-dependent clpX-like chaperone, mitochondrialATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrialClpX caseinolytic peptidase X homologClpX caseinolytic protease X homologEnergy-dependent regulator of proteolysisEPP2

Proteolysis: Recognition, unfolding, and translocation of substrate proteins into ClpP, leading to their degradation[2][3]. Non-proteolytic unfolding: CLPX can remodel substrates for activation (e.g., facilitating cofactor incorporation into ALAS for heme biosynthesis)[1]. Small molecule allosteric modulation (e.g., ONC201 alters selectivity by activating ClpP)[2]