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Mitochondrial Biology Lab

Dept of Biochemistry, Indian Institute of Science, Bangalore.

Dr. Patrick D' Silva

Professor

Ph.D: Indian Institute of Technology, Powai-Bombay

PDF: University of Wisconsin-Madison, USA

Research Summary

Our lab research focusses on uncovering the pathways of mitochondrial protein translocation, biogenesis and turnover in connection to various pathophysiological conditions. By utilizing yeast and mammalian model systems, my lab will investigate the key regulatory mechanisms of redox homeostasis, protein trafficking & folding and organellar life cycle using a combination of experimental tools from genetics and cell biology with biochemistry.

Highlights

  • Elucidated intricate organization & moonlighting functions of pre-sequence translocase
  • Characterized therapeutic potential of nanozymes against oxidative stress disorders

Elucidating the organization of pre-sequence translocase and mechanisms of protein translocation across the mitochondria. Our studies delineate firsttime intricate organization of human pre-sequence translocase, which is significantly different from the yeast system. Our finding highlights the presence of 3 different translocase machinery for protein import across the mitochondrial inner membrane. Two of the translocases (B1 & B2) are essential for constitutive functions and translocase A found to be oncogenic in nature. Moreover, we uncovered that one of the components of the presequence machinery is involved in regulating apoptotic pathways thus imparting the chemoresistance in cancer cells. Our research findings provided first-time a direct connection between translocation machinery and the development of tumorigenicity. Our future long-term goal is to: (1) characterize the mitochondrial import motor and translocation machinery; (2) elucidate the mechanism and regulation of import motor component’s interactions with TIM23 channel to understand fundamental aspects of the mitochondrial protein transport process with respect to mitochondrial biogenesis in higher organisms; 3) characterize the organization of carrier translocase in connection to mitochondrial inner membrane protein biogenesis.

Awards

NameOrganizationYear
SIR. C.V. RAMAN KARNATAKA STATE SCIENCE AWARD, LIFE SCIENCESGovernment of Karnataka, India2017
FELLOW OF NATIONAL ACADEMY OF SCIENCESNational Academy of Sciences (NASI), Allahabad2017
EXCELLENCE IN DRUG RESEARCH IN LIFE SCIENCESCSIR-Central Drug Research Institute, Lucknow.2016
NATIONAL BIOSCIENCE AWARDDepartment of Biotechnology, India2014
YOUNG RESEARCHER AWARDSir Dorabji Tata and allied Trust2012
SWARNAJAYANTHI FELLOWSHIP AWARD IN LIFE SCIENCESMinistry of Science and Technology, DST, India2012
BM BIRLA SCIENCE PRIZE AWARD FOR BIOLOGICAL SCIENCESBirla Science Foundation2011
SENIOR RESEARCH FELLOWSHIP IN BIOMEDICAL SCIENCESWellcome Trust Foundation-UK2007

Recent Publications

Saccharomyces cerevisiae DJ-1 paralogs maintain genome integrity through glycation repair of nucleic acids and proteins

Gautam Susarla, Priyanka Kataria, Amrita Kundu, Patrick D'Silva

eLife, 2023 Aug

Functional crosstalk between the TIM22 complex and YME1 machinery maintains mitochondrial proteostasis and integrity

Abhishek Kumar, Tejashree Pradip Waingankar, Patrick D'Silva

Journal of Cell Science, 2023 Jan

Double DJ-1 domain containing Arabidopsis DJ-1D is a robust macromolecule deglycase

Melvin Prasad*, Priyanka Kataria*, Sunayana Ningaraju, Radhika Buddidathi, Kondalarao Bankapalli, Swetha Chenna, Gautam Susarla, Radhika Venkatesan, Patrick D’Silva#, P. V. Shivaprasad#

New Phytologist, 2022 Jul

A journey through the gateway of polytopic inner membrane proteins: The carrier translocase machinery

Abhishek Kumar, Srujan Kumar Matta, Vigneshwaran R, Patrick D'Silva

Current Opinion in Physiology, 2022 Mar

Loss of Function of mtHsp70 Chaperone Variants Leads to Mitochondrial Dysfunction in Congenital Sideroblastic Anemia

Vinaya Vishwanathan, Patrick D'Silva

Frontiers in Cell and Developmental Biology, 2022 Feb