Unraveling the Intricate Organization of Mammalian Mitochondrial Presequence Translocases: Existence of Multiple Translocases for Maintenance of Mitochondrial Function

Sinha, Devanjan and Srivastava, Shubhi and Krishna, Lekshmi and D'Silva, Patrick (2014) Unraveling the Intricate Organization of Mammalian Mitochondrial Presequence Translocases: Existence of Multiple Translocases for Maintenance of Mitochondrial Function. In: MOLECULAR AND CELLULAR BIOLOGY, 34 (10). pp. 1757-1775.

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Abstract

Mitochondria are indispensable organelles implicated in multiple aspects of cellular processes, including tumorigenesis. Heat shock proteins play a critical regulatory role in accurately delivering the nucleus-encoded proteins through membrane-bound presequence translocase (Tim23 complex) machinery. Although altered expression of mammalian presequence translocase components had been previously associated with malignant phenotypes, the overall organization of Tim23 complexes is still unsolved. In this report, we show the existence of three distinct Tim23 complexes, namely, B1, B2, and A, involved in the maintenance of normal mitochondrial function. Our data highlight the importance of Magmas as a regulator of translocase function and in dynamically recruiting the J-proteins DnaJC19 and DnaJC15 to individual translocases. The basic housekeeping function involves translocases B1 and B2 composed of Tim17b isoforms along with DnaJC19, whereas translocase A is nonessential and has a central role in oncogenesis. Translocase B, having a normal import rate, is essential for constitutive mitochondrial functions such as maintenance of electron transport chain complex activity, organellar morphology, iron-sulfur cluster protein biogenesis, and mitochondrial DNA. In contrast, translocase A, though dispensable for housekeeping functions with a comparatively lower import rate, plays a specific role in translocating oncoproteins lacking presequence, leading to reprogrammed mitochondrial functions and hence establishing a possible link between the TIM23 complex and tumorigenicity.

Item Type:	Journal Article
Publication:	MOLECULAR AND CELLULAR BIOLOGY
Publisher:	AMER SOC MICROBIOLOGY
Additional Information:	Copyright for this article belongs to the AMER SOC MICROBIOLOGY, USA
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	10 Jun 2014 10:59
Last Modified:	10 Jun 2014 10:59
URI:	http://eprints.iisc.ac.in/id/eprint/49117

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