Mitochondrial HSP70 Chaperone System—The Influence of Post-Translational Modifications and Involvement in Human Diseases

Abstract

Since their discovery, heat shock proteins (HSPs) have been identified in all domains of life, which demonstrates their importance and conserved functional role in maintaining protein homeostasis. Mitochondria possess several members of the major HSP sub-families that perform essential tasks for keeping the organelle in a fully functional and healthy state. In humans, the mitochondrial HSP70 chaperone system comprises a central molecular chaperone, mtHSP70 or mortalin (HSPA9), which is actively involved in stabilizing and importing nuclear gene products and in refolding mitochondrial precursor proteins, and three co-chaperones (HSP70-escort protein 1—HEP1, tumorous imaginal disc protein 1—TID-1, and Gro-P like protein E—GRPE), which regulate and accelerate its protein folding functions. In this review, we summarize the roles of mitochondrial molecular chaperones with particular focus on the human mtHsp70 and its co-chaperones, whose deregulated expression, mutations, and post-translational modifications are often considered to be the main cause of neurological disorders, genetic diseases, and malignant growth.

Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury

“…They confirmed that neutralization of HSP70 or TLR4 and kinases inhibition avoids cardiac protection [267]. Remarkably, HSP70 is a key component of mitochondrial import, translocation and protein folding [268], which are essential functions for mitochondrial biogenesis.…”

HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy

“…Importantly, the overexpression of GRP75 (including HSPA9B or mortalin-2) is found in many human malignancies which is causally correlated with their invasive growth, metastasis spread and resistance to chemotherapy and radiotherapy [ 24 , 29 , 31 , 32 ] (see also Section 4.3 ). Tumoral GRP75 is known to contribute to the cancer stemness and EMT program that are associated with the aggressiveness and persistence of mammary gland carcinomas [ 29 , 33 , 34 ].…”

With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

“…Exciting new roles for chaperones and co-chaperones related to inflammation, autoimmune disorders, and the previously described diseases include mitochondrial and nuclear shuttling of cargo and chaperone activity within these organelles (Figure 1). We encourage the reader to consider several reviews that cover chaperone-organelle specific activities and their role in disease in greater detail [48][49][50][51][52][53][54][55][56].…”