Maternal-Fetal Mitochondrial Metabolism

About the Program

Few processes are as energy-demanding as the development of a fetus and it is the cell's mitochondria that play a central role in generating the energy that powers this development. Mitochondria are also a hub for inflammatory response to infection and other threats to a developing fetus. It is thus crucial to understand the role of mitochondria in preterm birth syndromes and consequently the Maternal-Fetal Mitochondrial Metabolism Unit investigates both normal function and dysfunction of mitochondria in development. Members of the unit include Siddhesh Aras, MBBS, PhD, and Neeraja Purandare, PhD.


  • Study of mitochondrial metabolism during development.
  • Analysis of mitochondrial function during preterm birth syndromes using animal models, cultured cells, and human samples.
  • Determination of mechanism by which mitochondria become dysfunctional in inflammation.

Research Highlights

  • We have shown that reduced levels of Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) are responsible for inflammation-induced mitochondrial dysfunction. Increasing the levels of MNRR1 either genetically or via specific activators rescues the defect. MNRR1 therefore is an attractive target for inflammatory mitochondrial pathologies.
  • MNRR1 rescues dysfunctional mitochondria owing to its biorganellar function as an activator of multiple homeostatic cellular pathways. These include: i) enhancing respiration (oxidative phosphorylation), ii) stimulating the mitochondrial unfolded protein response, ii) inhibiting apoptosis, a form of cell death, and iv) transcriptionally regulating stress-responsive genes.
  • Currently, we are investigating the subcellular mechanism by which MNRR1 functions as an anti-inflammatory target in placental pathologies using in vitro and in vivo

Select Publications

  • Lipopolysaccharide induces placental mitochondrial dysfunction by reducing MNRR1 levels via a TLR4-independent pathway. Purandare, Neeraja, Yusef Kunji, Yue Xi, Roberto Romero, Nardhy Gomez-Lopez, Andrew Fribley, Lawrence I. Grossman, and Siddhesh Aras. bioRxiv (2021) (in revision).
  • Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype in MELAS by inducing stress responsive homeostatic mechanisms. Aras S, Purandare N, Gladyck S, Somayajulu-Nitu M, Zhang K, Wallace DC, Grossman LI. ProcNatl Acad Sci USA, 2020in press.
  • Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors.Moreno-Domínguez A, Ortega-Sáenz P, Gao L, Colinas O, García-Flores P, Bonilla-Henao V, Aragonés J, Hüttemann M, Grossman LI, Weissmann N, Sommer N, López-Barneo J. Sci Signal. 2020 Jan 21; 13:eaay9452. PMID: 31848220
  • The cellular stress proteins CHCHD10 and MNRR1 (CHCHD2): Partners in mitochondrial and nuclear function and dysfunction.Purandare N, Somayajulu M, Hüttemann M, Grossman LI, Aras S. J Biol Chem. 2018 Apr 27; 293:6517-6529. PMID: 29540477
  • Metformin, the aspirin of the 21st century: its role in gestational diabetes, prevention of preeclampsia and cancer, and the promotion of longevity.Romero R, Erez O, Hüttemann M, Maymon E, Panaitescu B, Conde-Agudelo A, Pacora P, Yoon BH, Grossman LI. Am J Obstet Gynecol. 2017 Sep; 217:282-302. PMID:  28619690

Mitochondrial Section


  • The regulation of mitochondrial function during normal placental development
  • Delineation of the effects of inflammation on mitochondrial function in a cell and tissue culture model and characterization of a pathway for the observed effects


  • To understand how MNRR1 mediated mitochondrial function relates to organellar activity throughout pregnancy, and therefore the repercussions of an inflammatory insult on MNRR1-mediated mitochondrial dysfunction

Research Focus

  • How do inflammatory stimuli induce mitochondrial dysfunction?
  • What is the pathway by which LPS affects mitochondrial function?
  • How does stress regulator MNRR1 (CHCHD2) function during plaental inflammation?


  • In preliminary data, MNRR1 decreases duering placental inflammation, inhibiting mitochondrial function.