The role of mitochondria within a cell has grown beyond being the prime source of cellular energy to one of the major signaling platforms. Recent evidence provides several insights into the crucial roles of mitochondrial chaperones in regulating the organellar response to external triggers. The mitochondrial Hsp70 (mtHsp70/Mortalin/Grp75) chaperone system plays a critical role in the maintenance of proteostasis balance in the organelle. Defects in mtHsp70 network result in attenuated protein transport and misfolding of polypeptides leading to mitochondrial dysfunction. The functions of Hsp70 are primarily governed by J-protein cochaperones. Although human mitochondria possess a single Hsp70, its multifunctionality is characterized by the presence of multiple specific J-proteins. Several studies have shown a potential association of Hsp70 and J-proteins with diverse pathological states that are not limited to their canonical role as chaperones. The role of mitochondrial Hsp70 and its co-chaperones in disease pathogenesis has not been critically reviewed in recent years. We evaluated some of the cellular interfaces where Hsp70 machinery associated with pathophysiological conditions, particularly in context of tumorigenesis and neurodegeneration. The mitochondrial Hsp70 machinery shows a variable localization and integrates multiple components of the cellular processes with varied phenotypic consequences. Although Hsp70 and J-proteins function synergistically in proteins folding, their precise involvement in pathological conditions is mainly idiosyncratic. This machinery is associated with a heterogeneous set of molecules during the progression of a disorder. However, the precise binding to the substrate for a specific physiological response under a disease subtype is still an undocumented area of analysis.

细胞内线粒体的作用已从细胞能量的主要来源发展到主要的信号传递平台之一。最新证据为线粒体分子伴侣在调节细胞器对外部触发的反应中的关键作用提供了一些见解。线粒体Hsp70（mtHsp70 / Mortalin / Grp75）分子伴侣系统在维持细胞器蛋白质平衡方面起着至关重要的作用。mtHsp70网络中的缺陷导致减弱的蛋白运输和多肽错误折叠，导致线粒体功能障碍。Hsp70的功能主要由J蛋白伴侣蛋白支配。尽管人线粒体具有单个Hsp70，但其多功能性的特征是存在多个特定的J蛋白。几项研究表明，Hsp70和J蛋白与多种病理状态之间可能存在关联，这些状态不仅限于其作为伴侣的典型作用。近年来，线粒体Hsp70及其伴侣分子在疾病发病机理中的作用尚未得到严格的审查。我们评估了Hsp70机制与病理生理状况相关的某些细胞界面，特别是在肿瘤发生和神经退行性变的情况下。线粒体Hsp70机器显示出可变的定位，并整合了具有不同表型后果的细胞过程的多个组成部分。尽管Hsp70和J蛋白在蛋白折叠中具有协同作用，但它们在病理情况中的精确参与主要是特异的。在疾病发展过程中，这种机制与一组异质的分子有关。然而，在疾病亚型下针对特定生理反应与底物的精确结合仍然是未记录的分析领域。